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Zhang, Xueli, Hong Zhang, Chuanwen Fan, Camilla Hildesjö, Bairong Shen, and Xiao-Feng Sun. "Loss of CHGA Protein as a Potential Biomarker for Colon Cancer Diagnosis: A Study on Biomarker Discovery by Machine Learning and Confirmation by Immunohistochemistry in Colorectal Cancer Tissue Microarrays." Cancers 14, no. 11 (May 27, 2022): 2664. http://dx.doi.org/10.3390/cancers14112664.
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Background. The incidence of colorectal cancers has been constantly increasing. Although the mortality has slightly decreased, it is far from satisfaction. Precise early diagnosis for colorectal cancer has been a great challenge in order to improve patient survival. Patients and Methods. We started with searching for protein biomarkers based on our colorectal cancer biomarker database (CBD), finding differential expressed genes (GEGs) and non-DEGs from RNA sequencing (RNA-seq) data, and further predicted new biomarkers of protein–protein interaction (PPI) networks by machine learning (ML) methods. The best-selected biomarker was further verified by a receiver operating characteristic (ROC) test from microarray and RNA-seq data, biological network, and functional analysis, and immunohistochemistry in the tissue arrays from 198 specimens. Results. There were twelve proteins (MYO5A, CHGA, MAPK13, VDAC1, CCNA2, YWHAZ, CDK5, GNB3, CAMK2G, MAPK10, SDC2, and ADCY5) which were predicted by ML as colon cancer candidate diagnosis biomarkers. These predicted biomarkers showed close relationships with reported biomarkers of the PPI network and shared some pathways. An ROC test showed the CHGA protein with the best diagnostic accuracy (AUC = 0.9 in microarray data and 0.995 in RNA-seq data) among these candidate protein biomarkers. Furthermore, immunohistochemistry examination on our colon cancer tissue microarray samples further confirmed our bioinformatical prediction, indicating that CHGA may be used as a potential biomarker for early diagnosis of colon cancer patients. Conclusions. CHGA could be a potential candidate biomarker for diagnosing earlier colon cancer in the patients.
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Zhang, Xueli, Xiao-Feng Sun, Bairong Shen, and Hong Zhang. "Potential Applications of DNA, RNA and Protein Biomarkers in Diagnosis, Therapy and Prognosis for Colorectal Cancer: A Study from Databases to AI-Assisted Verification." Cancers 11, no. 2 (February 1, 2019): 172. http://dx.doi.org/10.3390/cancers11020172.
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In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.
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Fyfe, Ian. "RNA biomarkers of Parkinson disease." Nature Reviews Neurology 17, no. 3 (February 9, 2021): 132. http://dx.doi.org/10.1038/s41582-021-00470-3.
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Bustin, Stephen A., and Jamie Murphy. "RNA biomarkers in colorectal cancer." Methods 59, no. 1 (January 2013): 116–25. http://dx.doi.org/10.1016/j.ymeth.2012.10.003.
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Shahjaman, Md, Habiba Akter, Md Mamunur Rashid, Md Ibnul Asifuzzaman, Md Bipul Hossen, and Md Rezanur Rahman. "Robust and efficient identification of biomarkers from RNA-Seq data using median control chart." F1000Research 8 (January 3, 2019): 7. http://dx.doi.org/10.12688/f1000research.17351.1.
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Background: One of the main goals of RNA-seq data analysis is identification of biomarkers that are differentially expressed (DE) across two or more experimental conditions. RNA-seq uses next generation sequencing technology and it has many advantages over microarrays. Numerous statistical methods have already been developed for identification the biomarkers from RNA-seq data. Most of these methods were based on either Poisson distribution or negative binomial distribution. However, efficient biomarker identification from discrete RNA-seq data is hampered by existing methods when the datasets contain outliers or extreme observations. Specially, the performance of these methods becomes more severe when the data come from a small number of samples in the presence of outliers. Therefore, in this study, an attempt is made to propose an outlier detection and modification approach for RNA-seq data to overcome the aforesaid problems of traditional methods. We make our proposed method facilitate in RNA-seq data by transforming the read count data into continuous data. Methods: We use median control chart to detect and modify the outlying observation in a log-transformed RNA-seq dataset. To investigate the performance of the proposed method in absence and presence of outliers, we employ the five popular biomarker selection methods (edgeR, edgeR_robust, DEseq, DEseq2 and limma) both in simulated and real datasets. Results: The simulation results strongly suggest that the performance of the proposed method improved in the presence of outliers. The proposed method also detected an additional 18 outlying DE genes from a real mouse RNA-seq dataset that were not detected by traditional methods. Using the KEGG pathway and gene ontology analysis results we reveal that these genes may be biomarkers, which require validation in a wet lab. Conclusions: Our proposal is to apply the proposed method for biomarker identification from other RNA-seq data.
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Nikitina, A. S., V. V. Babenko, K. A. Babalyan, A. O. Vasiliev, A. V. Govorov, E. A. Prilepskaya, S. A. Danilenko, O. V. Selezneva, and E. I. Sharova. "Primary candidate RNA biomarker screening by RNA-seq for prostate cancer diagnostics." Biomeditsinskaya Khimiya 61, no. 6 (2015): 781–84. http://dx.doi.org/10.18097/pbmc20156106781.
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The RNA-seq approach for prostate cancer candidate RNA biomarkers screening in plasma and urine obtained by minimally invasive or noninvasive methods is proved to be feasible. Significant amount of RNA biomarkers associated with prostate cancer according to the literature were found in plasma and urine samples obtained from patients with benign prostatic hyperplasia (BPH). The number of detected markers was shown to vary in accordance with method of library preparation used for transcriptome profiling. The detection of known RNA biomarkers for prostate cancer in urine and plasma samples shows the feasibility of such method for minimally invasive diagnostics. The fact of presence of the same RNA biomarkers in samples from patients with BPH suggests their possible lack of specificity and confirms the need for further research in this area.
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Li, Feng, Janice M. Yoshizawa, Kyoung-Mee Kim, Julie Kanjanapangka, Tristan R. Grogan, Xiaoyan Wang, David E. Elashoff, et al. "Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer." Clinical Chemistry 64, no. 10 (October 1, 2018): 1513–21. http://dx.doi.org/10.1373/clinchem.2018.290569.
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Abstract BACKGROUND Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72–0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80–0.93). CONCLUSIONS We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.
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Dutton, Gail. "Singling Out RNA Biomarkers in Situ." Genetic Engineering & Biotechnology News 37, no. 6 (March 15, 2017): 4–5. http://dx.doi.org/10.1089/gen.37.06.04.
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Engelhardt, Stefan. "Small RNA Biomarkers Come of Age." Journal of the American College of Cardiology 60, no. 4 (July 2012): 300–303. http://dx.doi.org/10.1016/j.jacc.2012.04.018.
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Chauhan, Ranjit, and Nivedita Lahiri. "Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma." Biomarkers in Cancer 8s1 (January 2016): BIC.S34413. http://dx.doi.org/10.4137/bic.s34413.
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Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.
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Saunders, Matthew A., and Lee P. Lim. "(micro)Genomic medicine: microRNAs as therapeutics and biomarkers." RNA Biology 6, no. 3 (July 2009): 324–28. http://dx.doi.org/10.4161/rna.6.3.8871.
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Grunig, Gabriele, Aram Baghdassarian, Sung-Hyun Park, Serhiy Pylawka, Bertram Bleck, Joan Reibman, Erika Berman-Rosenzweig, and Nedim Durmus. "Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs." Biomarker Insights 10s4 (January 2015): BMI.S29514. http://dx.doi.org/10.4137/bmi.s29514.
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This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Biomarkers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling.
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Badimon, Lina, Emma L. Robinson, Amela Jusic, Irina Carpusca, Leon J. deWindt, Costanza Emanueli, Péter Ferdinandy, et al. "Cardiovascular RNA markers and artificial intelligence may improve COVID-19 outcome: a position paper from the EU-CardioRNA COST Action CA17129." Cardiovascular Research 117, no. 8 (April 11, 2021): 1823–40. http://dx.doi.org/10.1093/cvr/cvab094.
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Abstract The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells. Hence a significant proportion of infected patients develop cardiac events, such as arrhythmias and heart failure. Patients with cardiovascular comorbidities are at highest risk of cardiac death. To face the pandemic and limit its burden, health authorities have launched several fast-track calls for research projects aiming to develop rapid strategies to combat the disease, as well as longer-term projects to prepare for the future. Biomarkers have the possibility to aid in clinical decision-making and tailoring healthcare in order to improve patient quality of life. The biomarker potential of circulating RNAs has been recognized in several disease conditions, including cardiovascular disease. RNA biomarkers may be useful in the current COVID-19 situation. The discovery, validation, and marketing of novel biomarkers, including RNA biomarkers, require multi-centre studies by large and interdisciplinary collaborative networks, involving both the academia and the industry. Here, members of the EU-CardioRNA COST Action CA17129 summarize the current knowledge about the strain that COVID-19 places on the cardiovascular system and discuss how RNA biomarkers can aid to limit this burden. They present the benefits and challenges of the discovery of novel RNA biomarkers, the need for networking efforts, and the added value of artificial intelligence to achieve reliable advances.
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Bahn, Jae Hoon, Qing Zhang, Feng Li, Tak-Ming Chan, Xianzhi Lin, Yong Kim, David T. W. Wong, and Xinshu Xiao. "The Landscape of MicroRNA, Piwi-Interacting RNA, and Circular RNA in Human Saliva." Clinical Chemistry 61, no. 1 (January 1, 2015): 221–30. http://dx.doi.org/10.1373/clinchem.2014.230433.
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Abstract BACKGROUND Extracellular RNAs (exRNAs) in human body fluids are emerging as effective biomarkers for detection of diseases. Saliva, as the most accessible and noninvasive body fluid, has been shown to harbor exRNA biomarkers for several human diseases. However, the entire spectrum of exRNA from saliva has not been fully characterized. METHODS Using high-throughput RNA sequencing (RNA-Seq), we conducted an in-depth bioinformatic analysis of noncoding RNAs (ncRNAs) in human cell-free saliva (CFS) from healthy individuals, with a focus on microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and circular RNAs (circRNAs). RESULTS Our data demonstrated robust reproducibility of miRNA and piRNA profiles across individuals. Furthermore, individual variability of these salivary RNA species was highly similar to those in other body fluids or cellular samples, despite the direct exposure of saliva to environmental impacts. By comparative analysis of >90 RNA-Seq data sets of different origins, we observed that piRNAs were surprisingly abundant in CFS compared with other body fluid or intracellular samples, with expression levels in CFS comparable to those found in embryonic stem cells and skin cells. Conversely, miRNA expression profiles in CFS were highly similar to those in serum and cerebrospinal fluid. Using a customized bioinformatics method, we identified >400 circRNAs in CFS. These data represent the first global characterization and experimental validation of circRNAs in any type of extracellular body fluid. CONCLUSIONS Our study provides a comprehensive landscape of ncRNA species in human saliva that will facilitate further biomarker discoveries and lay a foundation for future studies related to ncRNAs in human saliva.
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Griswold, Anthony J., Jose Perez, Karen Nuytemans, Thomas Strong, Liyong Wang, Hayley Ennis, Marvin Smith, Jeffery Vance, Margaret A. Pericak-Vance, and Lee D. Kaplan. "Osteoarthritic Extracellular RNA Biomarkers in Synovial Fluid." Medicine & Science in Sports & Exercise 49, no. 5S (May 2017): 87–88. http://dx.doi.org/10.1249/01.mss.0000517066.47887.fb.
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Nilsson, R. Jonas A., Leonora Balaj, Esther Hulleman, Sjoerd van Rijn, D. Michiel Pegtel, Maudy Walraven, Anders Widmark, et al. "Blood platelets contain tumor-derived RNA biomarkers." Blood 118, no. 13 (September 29, 2011): 3680–83. http://dx.doi.org/10.1182/blood-2011-03-344408.
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Abstract Diagnostic platforms providing biomarkers that are highly predictive for diagnosing, monitoring, and stratifying cancer patients are key instruments in the development of personalized medicine. We demonstrate that tumor cells transfer (mutant) RNA into blood platelets in vitro and in vivo, and show that blood platelets isolated from glioma and prostate cancer patients contain the cancer-associated RNA biomarkers EGFRvIII and PCA3, respectively. In addition, gene-expression profiling revealed a distinct RNA signature in platelets from glioma patients compared with normal control subjects. Because platelets are easily accessible and isolated, they may form an attractive platform for the companion diagnostics of cancer.
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Qi, Xin, Yuxin Lin, Jiajia Chen, and Bairong Shen. "Decoding competing endogenous RNA networks for cancer biomarker discovery." Briefings in Bioinformatics 21, no. 2 (January 30, 2019): 441–57. http://dx.doi.org/10.1093/bib/bbz006.
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Abstract Crosstalk between competing endogenous RNAs (ceRNAs) is mediated by shared microRNAs (miRNAs) and plays important roles both in normal physiology and tumorigenesis; thus, it is attractive for systems-level decoding of gene regulation. As ceRNA networks link the function of miRNAs with that of transcripts sharing the same miRNA response elements (MREs), e.g. pseudogenes, competing mRNAs, long non-coding RNAs, and circular RNAs, the perturbation of crucial interactions in ceRNA networks may contribute to carcinogenesis by affecting the balance of cellular regulatory system. Therefore, discovering biomarkers that indicate cancer initiation, development, and/or therapeutic responses via reconstructing and analyzing ceRNA networks is of clinical significance. In this review, the regulatory function of ceRNAs in cancer and crucial determinants of ceRNA crosstalk are firstly discussed to gain a global understanding of ceRNA-mediated carcinogenesis. Then, computational and experimental approaches for ceRNA network reconstruction and ceRNA validation, respectively, are described from a systems biology perspective. We focus on strategies for biomarker identification based on analyzing ceRNA networks and highlight the translational applications of ceRNA biomarkers for cancer management. This article will shed light on the significance of miRNA-mediated ceRNA interactions and provide important clues for discovering ceRNA network-based biomarker in cancer biology, thereby accelerating the pace of precision medicine and healthcare for cancer patients.
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Talluri, Bhavana, Kshitij Amar, Michael Saul, Tasnim Shireen, Vjollca Konjufca, Jian Ma, Taekjip Ha, and Farhan Chowdhury. "COL2A1 Is a Novel Biomarker of Melanoma Tumor Repopulating Cells." Biomedicines 8, no. 9 (September 18, 2020): 360. http://dx.doi.org/10.3390/biomedicines8090360.
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Soft 3D-fibrin-gel selected tumor repopulating cells (TRCs) from the B16F1 melanoma cell line exhibit extraordinary self-renewal and tumor-regeneration capabilities. However, their biomarkers and gene regulatory features remain largely unknown. Here, we utilized the next-generation sequencing-based RNA sequencing (RNA-seq) technique to discover novel biomarkers and active gene regulatory features of TRCs. Systems biology analysis of RNA-seq data identified differentially expressed gene clusters, including the cell adhesion cluster, which subsequently identified highly specific and novel biomarkers, such as Col2a1, Ncam1, F11r, and Negr1. We validated the expression of these genes by real-time qPCR. The expression level of Col2a1 was found to be relatively low in TRCs but twenty-fold higher compared to the parental control cell line, thus making the biomarker very specific for TRCs. We validated the COL2A1 protein by immunofluorescence microscopy, showing a higher expression of COL2A1 in TRCs compared to parental control cells. KEGG pathway analysis showed the JAK/STAT, hypoxia, and Akt signaling pathways to be active in TRCs. Besides, the aerobic glycolysis pathway was found to be very active, indicating a typical Warburg Effect on highly tumorigenic cells. Together, our study revealed highly specific biomarkers and active cell signaling pathways of melanoma TRCs that can potentially target and neutralize TRCs.
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Pansarasa, Orietta, Maria Garofalo, Eveljn Scarian, Francesca Dragoni, Jessica Garau, Rosalinda Di Gerlando, Luca Diamanti, Matteo Bordoni, and Stella Gagliardi. "Biomarkers in Human Peripheral Blood Mononuclear Cells: The State of the Art in Amyotrophic Lateral Sclerosis." International Journal of Molecular Sciences 23, no. 5 (February 25, 2022): 2580. http://dx.doi.org/10.3390/ijms23052580.
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Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the progressive loss of lower motor neurons, weakness and muscle atrophy. ALS lacks an effective cure and diagnosis is often made by exclusion. Thus, it is imperative to search for biomarkers. Biomarkers can help in understanding ALS pathomechanisms, identification of targets for treatment and development of effective therapies. Peripheral blood mononuclear cells (PBMCs) represent a valid source for biomarkers compared to cerebrospinal fluid, as they are simple to collect, and to plasma, because of the possibility of detecting lower expressed proteins. They are a reliable model for patients’ stratification. This review provides an overview on PBMCs as a potential source of biomarkers in ALS. We focused on altered RNA metabolism (coding/non-coding RNA), including RNA processing, mRNA stabilization, transport and translation regulation. We addressed protein abnormalities (aggregation, misfolding and modifications); specifically, we highlighted that SOD1 appears to be the most characterizing protein in ALS. Finally, we emphasized the correlation between biological parameters and disease phenotypes, as regards prognosis, severity and clinical features. In conclusion, even though further studies are needed to standardize the use of PBMCs as a tool for biomarker investigation, they represent a promising approach in ALS research.
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Li, Peiyao, Zihao Xu, Tao Liu, Qing Liu, Hecheng Zhou, Shujuan Meng, Ziyang Feng, et al. "Circular RNA Sequencing Reveals Serum Exosome Circular RNA Panel for High-Grade Astrocytoma Diagnosis." Clinical Chemistry 68, no. 2 (January 27, 2022): 332–43. http://dx.doi.org/10.1093/clinchem/hvab254.
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Abstract Background Although major advances have been made in the histopathological diagnosis of high-grade astrocytoma (HGA), methods for effective and noninvasive diagnosis remain largely unknown. Exosomes can cross the blood–brain barrier and are readily accessible in human biofluids, making them promising biomarkers for HGA. Circular RNAs (circRNAs) have potential as tumor biomarkers owing to their stability, conservation, and tissue specificity. However, the landscape and characteristics of exosome circRNAs in HGA remain to be studied. Methods CircRNA deep sequencing and bioinformatics approaches were used to generate a circRNA profiling database and analyze the features of HGA cell circRNAs and HGA cell-derived exosome circRNAs. Exosome circRNA expression in the serum and tissues of healthy individuals and patients with HGA was detected using reverse transcription-quantitative PCR. Additionally, the receiver operating characteristic curve and overall survival curves were analyzed. Results By investigating the characteristics of HGA cell-derived exosome circRNAs and HGA cell circRNAs, we observed that exosomes were more likely to enrich short-exon and suppressor circRNAs than HGA cells. Moreover, a serum exosome circRNA panel including hsa_circ_0075828, hsa_circ_0003828, and hsa_circ_0002976 could be used to screen for HGA, whereas a good prognosis panel comprised high concentrations of hsa_circ_0005019, hsa_circ_0000880, hsa_circ_0051680, and hsa_circ_0006365. Conclusions This study revealed a comprehensive circRNA landscape in HGA exosomes and cells. The serum exosome circexosome circRNA panel and tissue circRNAs are potentially useful for HGA liquid biopsy and prognosis monitoring. Exosome circRNAs as novel targets should facilitate further biomarker discovery and aid in HGA diagnosis and therapy monitoring.
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Cinque, Alessandra, Riccardo Vago, and Francesco Trevisani. "Circulating RNA in Kidney Cancer: What We Know and What We Still Suppose." Genes 12, no. 6 (May 28, 2021): 835. http://dx.doi.org/10.3390/genes12060835.
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Renal cancer represents the 7th most common tumor worldwide, affecting 400,000 people annually. This malignancy, which is the third most frequent cancer among urological diseases, displays a completely different prognosis if the tumor is detected in the early stages or advance phases. Unfortunately, more than 50% of renal cancers are discovered incidentally, with a consistent percentage of cases where the tumor remains clinically silent till the metastatic process is established. In day-to-day clinical practice, no available predictive biomarkers exist, and the existent imaging diagnostic techniques harbor several gaps in terms of diagnosis and prognosis. In the last decade, many efforts have been reported to detect new predictive molecular biomarkers using liquid biopsies, which are less invasive in comparison to renal biopsy. However, until now, there has been no clear evidence that a liquid biopsy biomarker could be relevant to the creation of a precise and tailored medical management in these oncological patients, even though circulating RNA biomarkers remain among the most promising. Given the idea that liquid biopsies will play a future key role in the management of these patients, in the present review, we summarize the current state of circulating RNA (miRNA, lncRNAs, and circRNAs) as possible biomarkers of renal cancer presence and aggressiveness in patients.
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Han, Henry, and Xiaoqian Jiang. "Disease Biomarker Query from RNA-Seq Data." Cancer Informatics 13s1 (January 2014): CIN.S13876. http://dx.doi.org/10.4137/cin.s13876.
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As a revolutionary way to unveil transcription, RNA-Seq technologies are challenging bioinformatics for its large data volumes and complexities. A large number of computational models have been proposed for differential expression (DE) analysis and normalization from different standing points. However, there were no studies available yet to conduct disease biomarker discovery for this type of high-resolution digital gene expression data, which will actually be essential to explore its potential in clinical bioinformatics. Although there were many biomarker discovery algorithms available in traditional omics communities, they cannot be applied to RNA-Seq count data to seek biomarkers directly for its special characteristics. In this work, we have presented a biomarker discovery algorithm, SEQ-Marker for RNA-Seq data, which is built on a novel data-driven feature selection algorithm, nonnegative singular value approximation (NSVA), which contributes to the robustness and sensitivity of the following DE analysis by taking advantages of the built-in characteristics of RNA-Seq count data. As a biomarker discovery algorithm built on network marker topology, the proposed SEQ-Marker not only bridges transcriptomics and systems biology but also contributes to clinical diagnostics.
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Gaston, Sandra M., Johan K. Skog, Benjamin Spieler, Alan Dal Pra, Radka Stoyanova, Christian Fischer, Yevgenia Khodor, et al. "Abstract 3492: Exosome-based plasma RNA biomarkers for high-risk prostate cancer." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3492. http://dx.doi.org/10.1158/1538-7445.am2022-3492.
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Abstract Introduction: There is an unmet need for liquid biopsy tests to support the management of patients with intermediate and high-risk prostate cancer (PCa). In treatment naïve patients, risk stratification by standard pathology and tissue based genomic testing can be influenced by sampling errors inherent to PCa biopsy. Exosome-based liquid biopsies are emerging as a clinically effective platform for minimally invasive and highly sensitive diagnostics for diverse types of cancer. In this project we undertake the development of a plasma exosome-based liquid biopsy to stratify patients with clinically significant PCa that may circumvent the sampling challenges associated with tissue-based genomic tests. Exosomes are small double-lipid membrane vesicles that cells actively shed into various biofluids and that provide stable packages for RNA, DNA and protein molecules. Here we take advantage of a well-developed exosomal biomarker analysis platform to profile plasma exosomal RNA markers that differentiate treatment-naïve men diagnosed with NCCN low risk vs high risk PCa as the first step in the development of a plasma exosomal liquid biopsy to support the management of patients with intermediate and high-risk disease. Methods: We compared plasma exosomal RNA profiles from 11 high-risk and 9 low-risk, treatment-naïve, biopsy-confirmed patients together with 4 healthy controls. Exosomes were isolated from 1 ml plasma samples and exosomal RNA prepared using the ExosomeDx ExoLution platform. A hybrid-capture RNA Next Generation Sequencing analysis was performed to enrich for transcripts of exons, 3’ and 5’ untranslated RNA and long non-coding RNA (lncRNA) to identify differentially expressed RNAs. Results: We detected over 10,000 protein coding genes and ~400 lncRNAs in each plasma sample using exosomal RNAseq. 273 genes were differentially expressed between high-risk vs control but not in low-risk vs control. We identified four potential plasma exosomal biomarkers of high-risk PCa. These include three protein coding mRNA transcripts that showed greater than 20-fold lower expression in plasma from high-risk in comparison to low-risk patients; TCGA data show that two of these mRNA markers are also downregulated in PCa tissue in patients with worse survival. In addition, we identified one lncRNA that showed greater than 20-fold higher expression in plasma from high-risk in comparison to low-risk patients. We also detected multiple alternate androgen receptor transcripts in plasma exosomal RNA from the high-risk patients. Together, these represent early data for potentially novel liquid biopsy RNA biomarkers for high-risk PCa. Conclusions: Here we report results of a liquid biopsy biomarker discovery study to develop an exosome-based long RNA test for to support the management of patients with intermediate and high-risk PCa. Plasma exosomal RNA provides a rich reservoir of currently untapped biomarkers for high-risk PCa. Citation Format: Sandra M. Gaston, Johan K. Skog, Benjamin Spieler, Alan Dal Pra, Radka Stoyanova, Christian Fischer, Yevgenia Khodor, Grannum Sant, Seth Yu, Vasisht Tadigotla, Sudipto K. Chakrabortty, Sanoj Punnen, Alan Pollack. Exosome-based plasma RNA biomarkers for high-risk prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3492.
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Miura, Norimasa, Junichi Hasegawa, and Goshi Shiota. "Serum Messenger RNA as a Biomarker and its Clinical Usefulness in Malignancies." Clinical medicine. Oncology 2 (January 2008): CMO.S379. http://dx.doi.org/10.4137/cmo.s379.
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A number of biomarkers are used clinically and many protein-based assay methods are available. Improvements in the method to utilize specific antibodies have led to remarkable progress in clinical diagnosis using biomarkers. Proteomics studies to identify better biomarkers have been performed worldwide by using a protein-based comprehensive method. The detection rate of conventional biomarkers can not improve further. Now is a time that a breakthrough is needed. We previously proposed mRNA, which is circulating in the body, as a novel material for biomarkers. mRNA is an unexpectedly useful molecule, not only because it can detect genes with a low expression level in protein, but also because it can detect the expression from non-coding RNA precursor genes or gene products with limited secretion from the cells. Circulating mRNA has been thought to be unstable in blood containing RNase. We confirm that mRNA remains at the same level for 24 hours after blood sampling. Unlike DNA, the RNA molecule can reflect events in the human body which occurred within a day, resulting in an early diagnosis of diseases. We report the possibility to detect and quantify cancer-derived mRNAs circulating in human vessels. We introduce the detection of serum mRNA as a useful biomarker of human malignancies. Abbreviations hTERT: human telomerase reverse transcriptase protein; HCC: hepatocellular carcinoma; hTR: human telomerase RNA template; HCV: hepatitis C virus; HBV: hepatitis B virus; AH: adenomatous hyperplasia; AAH: atypical adenomatous hyperplasia; LC: liver cirrhosis; CH: chronic hepatitis; AFP: α-fetoprotein; DCP; des-γ-carboxy prothrombin; ALT: alanine aminotransferase; Alb: albumin; EGFR: Epidermal growth factor receptor; non-small cell lung cancer; NSCLC: non-small cell lung cancer; small cell lung cancer; SCLC; ADC: adenocarcinoma; SCC: squamous cell carcinoma antigen; SqCC: squamous cell carcinoma; CEA: carcinoembryonic antigen; CYFRA (21–1): cytokeratin 19 fragment; CNA: circulating nucleic acids.
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Beylerli, O. A., A. T. Beylerli, and I. F. Gareev. "Long Non-Coding RNA as the Newest Perspective Biomarkers in Cancer." Innovative medicine of Kuban 14, no. 2 (June 22, 2019): 76–83. http://dx.doi.org/10.35401/2500-0268-2019-14-2-76-83.
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Long non-coding RNAs (lncRNAs) are a large group of non-coding RNAs (ncRNAs) which are more than 200 nucleotides in length. LncRNAs, as regulation factors, show an important role in complex cellular processes, such as apoptosis, growth, differentiation, proliferation, etc. Recently, the results of many studies have also shown their significant role in carcinogenesis. Endogenous lncRNAs are known to be secreted by tumor cells in human biological fluids in the form of microvesicles, exosomes, or protein complexes, thereby forming circulating lncRNAs that do not degrade under the influence of RNases and are in a stable state. Compared with traditional biomarkers, as proteins circulating lncRNA have several advantages that will allow to consider circulating lncRNA as a new potential biomarker for various diseases. Aberrant expression of lncRNAs was observed in cancer patients. In this context, endogenous lncRNAs can regulate the main characteristics of cancer cells, controlling the expression of oncogenes associated with their suppressive and oncogenic functions. Consequently, circulating lncRNAs can be excellent biomarkers for cancer. Knowledge of the molecular mechanisms by which lncRNAs contribute to the development of cancer will improve our understanding of etiology, and open up horizons for the development of new biomarkers. In this paper, we will analyze current knowledge about the change in the expression profile of circulating lncRNAs in cancer, as well as methods for their detection.
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Delmonico, Lucas, Said Attiya, Joan W. Chen, John C. Obenauer, Edward C. Goodwin, and Marcia V. Fournier. "Expression Concordance of 325 Novel RNA Biomarkers between Data Generated by NanoString nCounter and Affymetrix GeneChip." Disease Markers 2019 (May 14, 2019): 1–12. http://dx.doi.org/10.1155/2019/1940347.
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Background. With the development of new drug combinations and targeted treatments for multiple types of cancer, the ability to stratify categories of patient populations and to develop companion diagnostics has become increasingly important. A panel of 325 RNA biomarkers was selected based on cancer-related biological processes of healthy cells and gene expression changes over time during nonmalignant epithelial cell organization. This “cancer in reverse” approach resulted in a panel of biomarkers relevant for at least 7 cancer types, providing gene expression profiles representing key cellular signaling pathways beyond mutations in “driver genes.” Objective. To further investigate this biomarker panel, the objective of the current study is to (1) validate the assay reproducibility for the 325 RNA biomarkers and (2) compare gene expression profiles side by side using two technology platforms. Methods and Results. We have mapped the 325 RNA transcripts and in a custom NanoString nCounter expression panel to be compared to all potential probe sets in the Affymetrix Human Genome U133 Plus 2.0. The experiments were conducted with 10 unique biological formalin-fixed paraffin-embedded (FFPE) breast tumor samples. Each site extracted RNA from four sections of 10-micron thick FFPE tissue over three different days by two different operators using an optimized standard operating procedure and quality control criteria. Samples were analyzed using mas5 in BioConductor and NanoStringNorm in R. Pearson correlation showed reproducibility between sites for all 60 samples with r=0.995 for Affymetrix and r=0.999 for NanoString. Correlation in multiple days and multiple users was for Affymetrix r=0.962−0.999 and for NanoString r=0.982−0.991. Conclusion. The 325 RNA biomarkers showed reproducibility in two technology platforms with moderate to high concordance. Future directions include performing clinical validation studies and generating rationale for patient selection in clinical trials using the technically validated assay.
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Gu, Cuifeng, Guojian He, and Chenhong Lin. "REFINEMENT OF SALIVA MI-RNA BIOMARKERS FOR SPORT-RELATED CONCUSSION." Revista Brasileira de Medicina do Esporte 28, no. 5 (October 2022): 469–73. http://dx.doi.org/10.1590/1517-8692202228052022_126.
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ABSTRACT Introduction: The changes in brain structure caused by a sports-related concussion may initially be indistinguishable, however, the irreversible deleterious effects are noted in the long term. An early diagnosis may provide the patient with a better recovery chance and increased survival. For this purpose, this paper studies the feasibility of a diagnosis for concussion by microRNA (mi-RNA) biomarkers contained in the saliva of athletes. Objective: Verify whether salivary miRNAs could be considered good biomarkers for sports concussion. Methodology: Salivary mi-RNA levels were determined from 120 saliva samples of 120 players. There were 43 with a diagnosis of concussion and 77 without a diagnosis of concussion. Samples from players with a concussion were collected 30 minutes prior to activity, samples from individuals who did not engage in physical activity were also compared. Results: On the evaluation of 30 miRNA from individuals with a concussion between contact and non-contact sports there was high detection reliability(P<.05). Both miR-532-5p and miR-182-5p showed reduced amounts of physical activity. The miRNA-532-5p and miRNA-182-5p show significant results among 43 subjects from pre-exercise to post-exercise. The miRNA-4510 showed a significant result (p < 0.05) between contact and non-contact sport types. The amount of miRNA-4510 expanded in 20 individuals in the contact sport at post-exercise but remained normal in the non-contact sports group. Conclusion: The salivary miRNAs are reliable biomarkers for concussion. Evidence Level II; Therapeutic Studies – Investigating the results.
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Buonaurio, Flavia, Maria Luisa Astolfi, Daniela Pigini, Giovanna Tranfo, Silvia Canepari, Antonio Pietroiusti, Iacopo D’Alessandro, and Renata Sisto. "Oxidative Stress Biomarkers in Urine of Metal Carpentry Workers Can Be Diagnostic for Occupational Exposure to Low Level of Welding Fumes from Associated Metals." Cancers 13, no. 13 (June 24, 2021): 3167. http://dx.doi.org/10.3390/cancers13133167.
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Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO2Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.
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Salamin, Olivier, Emeric Gottardo, Céline Schobinger, Gemma Reverter-Branchat, Jordi Segura, Martial Saugy, Tiia Kuuranne, Jean-Daniel Tissot, Bernard Favrat, and Nicolas Leuenberger. "Detection of Stimulated Erythropoiesis by the RNA-Based 5'-Aminolevulinate Synthase 2 Biomarker in Dried Blood Spot Samples." Clinical Chemistry 65, no. 12 (December 1, 2019): 1563–71. http://dx.doi.org/10.1373/clinchem.2019.306829.
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Abstract BACKGROUND Despite implementation of the Athlete Biological Passport 10 years ago, blood doping remains difficult to detect. Thus, there is a need for new biomarkers to increase the sensitivity of the adaptive model. Transcriptomic biomarkers originating from immature reticulocytes may be reliable indicators of blood manipulations. Furthermore, the use of dried blood spots (DBSs) for antidoping purposes constitutes a complementary approach to venous blood collection. Here, we developed a method of quantifying the RNA-based 5′-aminolevulinate synthase 2 (ALAS2) biomarker in DBS. MATERIALS The technical, interindividual, and intraindividual variabilities of the method, and the effects of storage conditions on the production levels of ALAS2 RNA were assessed. The method was used to monitor erythropoiesis stimulated endogenously (blood withdrawal) or exogenously (injection of recombinant human erythropoietin). RESULTS When measured over a 7-week period, the intra- and interindividual variabilities of ALAS2 expression in DBS were 12.5%–42.4% and 49%, respectively. Following withdrawal of 1 unit of blood, the ALAS2 RNA in DBS increased significantly for up to 15 days. Variations in the expression level of this biomarker in DBS samples were more marked than those of the conventional hematological parameters, reticulocyte percentage and immature reticulocyte fraction. After exogenous stimulation of erythropoiesis via recombinant human erythropoietin injection, ALAS2 expression in DBS increased by a mean 8-fold. CONCLUSIONS Monitoring of transcriptomic biomarkers in DBS could complement the measurement of hematological parameters in the Athlete Biological Passport and aid the detection of blood manipulations.
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D’Ambrosi, Silvia, Allerdien Visser, Mafalda Antunes-Ferreira, Ankie Poutsma, Stavros Giannoukakos, Nik Sol, Siamack Sabrkhany, et al. "The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer." Cancers 13, no. 18 (September 16, 2021): 4644. http://dx.doi.org/10.3390/cancers13184644.
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Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.
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Long, Jintao, Genhua Pan, Emmanuel Ifeachor, Robert Belshaw, and Xinzhong Li. "Discovery of Novel Biomarkers for Alzheimer’s Disease from Blood." Disease Markers 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/4250480.
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Blood-based biomarkers for Alzheimer’s disease would be very valuable because blood is a more accessible biofluid and is suitable for repeated sampling. However, currently there are no robust and reliable blood-based biomarkers for practical diagnosis. In this study we used a knowledge-based protein feature pool and two novel support vector machine embedded feature selection methods to find panels consisting of two and three biomarkers. We validated these biomarker sets using another serum cohort and an RNA profile cohort from the brain. Our panels included the proteins ECH1, NHLRC2, HOXB7, FN1, ERBB2, and SLC6A13 and demonstrated promising sensitivity (>87%), specificity (>91%), and accuracy (>89%).
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Kitiyakara, Taya. "Advances in biomarkers for HCC." Thai Journal of Hepatology 1, no. 2 (May 31, 2018): 29–32. http://dx.doi.org/10.30856/th.jhep2018vol1iss2_07.
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Hepatocellular carcinoma is a common cancer worldwide and has a high mortality. Many patientspresent in the late stages and the outcome of treatment for these patients is poor. Biomarkerscould theoretically help to detect the disease at an earlier stage before symptoms occurand improve the treatment outcomes. The first biomarker found was alpha-fetoprotein (AFP) and it iscurrently used as part of the HCC surveillance recommended in many countries. However AFP isnot very accurate and 30-40% of HCCs may be missed. Currently there are other biomarkers underinvestigation. Most of the more common biomarkers studied are serum/blood tests and include AFP-L3,PIVKA-II, Glypican-2, VEGF and the non-coding RNAs, such as long non-coding RNA and microRNA,and metabolomics tests. Tests involving urine or patient breaths are still relatively uncommonbut are being investigated. The limitation on the use of these new biomarkers is from the availabilityand costs of the tests. Only AFP-L3 and PIVKA-II are currently commercially available.
Keywords: Biomarker, hepatocellular carcinoma, alpha-fetoprotein, microRNA, screening
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Tan, Chang, Jingyi Cao, Lu Chen, Xiaochen Xi, Siqi Wang, Yumin Zhu, Liuqing Yang, et al. "Noncoding RNAs Serve as Diagnosis and Prognosis Biomarkers for Hepatocellular Carcinoma." Clinical Chemistry 65, no. 7 (July 1, 2019): 905–15. http://dx.doi.org/10.1373/clinchem.2018.301150.
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Abstract BACKGROUND Reliable noninvasive biomarkers for hepatocellular carcinoma (HCC) diagnosis and prognosis are urgently needed. We explored the potential of not only microRNAs (miRNAs) but other types of noncoding RNAs (ncRNAs) as HCC biomarkers. METHODS Peripheral blood samples were collected from 77 individuals; among them, 57 plasma cell-free RNA transcriptomes and 20 exosomal RNA transcriptomes were profiled. Significantly upregulated ncRNAs and published potential HCC biomarkers were validated with reverse transcription (RT)-qPCR in an independent validation cohort (60–150 samples). We particularly investigated the diagnosis and prognosis performance and biological function for 1 ncRNA biomarker, RN7SL1, and its S fragment. RESULTS We identified certain circulating ncRNAs escaping from RNase degradation, possibly through binding with RNA-binding proteins: 899 ncRNAs were highly upregulated in HCC patients. Among them, 337 genes were fragmented long noncoding RNAs, 252 genes were small nucleolar RNAs, and 134 genes were piwi-interacting RNAs. Forty-eight candidates were selected and validated with RT-qPCR, of which, 16 ncRNAs were verified to be significantly upregulated in HCC, including RN7SL1, SNHG1, ZFAS1, and LINC01359. Particularly, the abundance of RN7SL1 S fragment discriminated HCC samples from negative controls (area under the curve, 0.87; 95% CI, 0.817–0.920). HCC patients with higher concentrations of RN7SL1 S fragment had lower survival rates. Furthermore, RN7SL1 S fragment alone promoted cancer cell proliferation and clonogenic growth. CONCLUSIONS Our results show that various ncRNA species, not only miRNAs, identified in the small RNA sequencing of plasma are also able to serve as noninvasive biomarkers. Particularly, we identified a domain of srpRNA RN7SL1 with reliable clinical performance for HCC diagnosis and prognosis.
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Xi, Xiaochen, Tianxiao Li, Yiming Huang, Jiahui Sun, Yumin Zhu, Yang Yang, and Zhi Lu. "RNA Biomarkers: Frontier of Precision Medicine for Cancer." Non-Coding RNA 3, no. 1 (February 20, 2017): 9. http://dx.doi.org/10.3390/ncrna3010009.
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Enache, Liviu, Elena Enache, Christophe Ramière, Olivier Diaz, Ligia Bancu, Anca Sin, and Patrice André. "Circulating RNA Molecules as Biomarkers in Liver Disease." International Journal of Molecular Sciences 15, no. 10 (September 30, 2014): 17644–66. http://dx.doi.org/10.3390/ijms151017644.
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Paneni, Francesco, and Massimo Volpe. "Exploring RNA biomarkers in patients with acute myocarditis." European Heart Journal 42, no. 35 (August 5, 2021): 3425–26. http://dx.doi.org/10.1093/eurheartj/ehab435.
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Lee, Khui Hung, Yong Song, Michael O'Sullivan, Jessica Metcalfe, Richard Loh, and Guicheng (Brad) Zhang. "RNA sequencing profiling potential biomarkers for nut allergy." World Allergy Organization Journal 13, no. 8 (August 2020): 100408. http://dx.doi.org/10.1016/j.waojou.2020.100408.
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Zvetkova, Elissaveta, and Georgi Kostov. "Extracellular RNA Biomarkers: New Development of Old Conception." Clinical Immunology 135 (January 2010): S81. http://dx.doi.org/10.1016/j.clim.2010.03.245.
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Martignano, Filippo, Lorena Rossi, Antonio Maugeri, Valentina Gallà, Vincenza Conteduca, Ugo De Giorgi, Valentina Casadio, and Giuseppe Schepisi. "Urinary RNA-based biomarkers for prostate cancer detection." Clinica Chimica Acta 473 (October 2017): 96–105. http://dx.doi.org/10.1016/j.cca.2017.08.009.
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van der Laan, Siem, Nicolas Salvetat, Dinah Weissmann, and Franck Molina. "Emerging RNA editing biomarkers will foster drug development." Drug Discovery Today 22, no. 7 (July 2017): 1056–63. http://dx.doi.org/10.1016/j.drudis.2017.01.017.
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Lan, Xiabin, Jiajie Xu, Chao Chen, Chuanming Zheng, Jiafeng Wang, Jun Cao, Xuhang Zhu, and Minghua Ge. "The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing." Cellular Physiology and Biochemistry 47, no. 3 (2018): 1122–32. http://dx.doi.org/10.1159/000490188.
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Background/Aims: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. Methods: High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. Results: We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776–, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895– being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047–, chr9: 16435553-16437522–, and chr22: 36006931-36007153– being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. Conclusions: Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis.
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D’Ambrosi, Silvia, R. Jonas Nilsson, and Thomas Wurdinger. "Platelets and tumor-associated RNA transfer." Blood 137, no. 23 (May 3, 2021): 3181–91. http://dx.doi.org/10.1182/blood.2019003978.
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Abstract Until recently, the nucleic acid content of platelets was considered to be fully determined by their progenitor megakaryocyte. However, it is now well understood that additional mediators (eg, cancer cells) can intervene, thereby influencing the RNA repertoire of platelets. Platelets are highly dynamic cells that are able to communicate and influence their environment. For instance, platelets have been involved in various steps of cancer development and progression by supporting tumor growth, survival, and dissemination. Cancer cells can directly and/or indirectly influence platelet RNA content, resulting in tumor-mediated “education” of platelets. Alterations in the tumor-educated platelet RNA profile have been described as a novel source of potential biomarkers. Individual platelet RNA biomarkers as well as complex RNA signatures may be used for early detection of cancer and treatment monitoring. Here, we review the RNA transfer occurring between cancer cells and platelets. We explore the potential use of platelet RNA biomarkers as a liquid biopsy biosource and discuss methods to evaluate the transcriptomic content of platelets.
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Krishnan, Preethi, Farooq Syed, Nicole Jiyun Kang, Raghavendra G. Mirmira, and Carmella Evans-Molina. "Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes." International Journal of Molecular Sciences 20, no. 23 (November 25, 2019): 5903. http://dx.doi.org/10.3390/ijms20235903.
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Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change ≥1.3 and a p-value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.
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Gregory, Andrew, Zhonghui Xu, Katherine Pratte, Seth Berman, Robin Lu, Rahul Suryadevara, Robert Chase, et al. "Blood RNA and protein biomarkers are associated with vaping and dual use, and prospective health outcomes." F1000Research 12 (February 2, 2023): 123. http://dx.doi.org/10.12688/f1000research.128583.1.
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Background: Electronic nicotine delivery systems (ENDS) are driving an epidemic of vaping. Identifying biomarkers of vaping and dual use (concurrent vaping and smoking) will facilitate studies of the health effects of vaping. To identify putative biomarkers of vaping and dual use, we performed association analysis in an observational cohort of 3,892 COPDGene study participants with blood transcriptomics and/or plasma proteomics data and self-reported current vaping and smoking behavior. Methods: Biomarkers of vaping and dual use were identified through differential expression analysis and related to prospective health events over six years of follow-up. To assess the predictive accuracy of multi-biomarker panels, we constructed predictive models for vaping and smoking categories and prospective health outcomes. Results: We identified three transcriptomic and three proteomic associations with vaping, and 90 transcriptomic and 100 proteomic associations to dual use. Many of these vaping or dual use biomarkers were significantly associated with prospective health outcomes, such as FEV1 decline (three transcripts and 62 proteins), overall mortality (18 transcripts and 73 proteins), respiratory mortality (two transcripts and 23 proteins), respiratory exacerbations (13 proteins) and incident cardiovascular disease (24 proteins). Multimarker models showed good performance discriminating between vaping and smoking behavior and produced informative, modestly powerful predictions of future FEV1 decline, mortality, and respiratory exacerbations. Conclusions: In summary, vaping and dual use are associated with RNA and protein blood-based biomarkers that are also associated with adverse health outcomes.
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Tabellini, Laura, Wenhong Fan, Lue Ping Zhao, and John A. Hansen. "Identifying Biomarkers for Acute GVHD." Blood 108, no. 11 (November 16, 2006): 38. http://dx.doi.org/10.1182/blood.v108.11.38.38.
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Abstract Acute graft versus host disease (aGVHD) is a complication of allogeneic hematopoietic cell transplantation (HCT). Current prevention and treatment approaches are effective in many but not all cases. Acute GVHD after a myeloablative HCT has a median onset of ~21 days, with a few cases occurring as late as 3 months post-HCT. We hypothesized that global gene expression profiling of RNA from white blood cells (WBC) could identify biomarkers associated with onset of aGVHD and potentially provide insight into the mechanisms responsible for causing clinically significant aGVHD. Patients were enrolled prospectively and blood samples collected weekly until onset of aGVHD or day 90. RNA samples adequate for hybridization were collected between day 19 and 24 from 23 patients who developed aGVHD (GVHD+) and compared with RNA from 13 patients who remained free of aGVHD through day 90 (GVHD−). All blood samples from GVHD+ patients were obtained prior to initiation of steroid therapy. Biotin-labeled cRNA was hybridized on Affymetrix HG-U133A. Realizing quantitative complexities underlying gene expression assessment and different assumptions required by different algorithms, we used 5 different summary algorithms (Mas5, PLIER, RMA, gcRMA, Dchip) to compute gene expression levels. Subsequently, we carried out analyses and identified genes that were consistently identified in more than one analyses; replications imply robustness of discoveries, even though discovery efficiency is compromised to some degree. A total of 141 genes showing differential expression were discovered. Thirteen functional classes were identified for 101 genes. The remaining 40 genes had unknown function. Sixteen transcription factors were identified, 12 of them showing increased expression such as the early response genes EGR1, EGR2, FOS and JUN. Among 12 immune response genes identified increased expression was observed for CD83 and IL-18, associated with antigen presentation and adaptive immunity; and NRS2, MMP9 and CD157, associated with innate immune response. Decreased expression was observed for CD52 and PTPN11. Among 7cell cycle progression and proliferation genes, we observed increased expression for CSF2, VEGF, PTN and TGFa. These data are consistent with the hypothesis that the development of acute GVHD is associated with acute inflammation. Ongoing validation studies using Taqman have confirmed up regulation of CD83 and EGR2 and down regulation of CD52 in GVHD+ patients. To further understand the functional implications of the 141 genes identified, probe sets were also input into Ingenuity Pathway Analysis software to identify possible signaling and regulatory pathways. The Ingenuity defined pathways most densely populated by the 141 genes included pathways controlling cytokine production and inflammation. Network analysis showed upregulation of transcriptional pathways responsible for cell proliferation, growth and activation: IL18, CSF2, TGFa and the transcription factors EGR1, EGR2, FOS and JUN were linked to networks that appear to have important role in regulation of expression of VEGF suggesting that it may be involved in sustaining inflammatory response in GVHD. This study demonstrates that whole genome transcriptional analysis of WBC RNA can be informative for detecting biomarkers associated with aGVHD. Furthermore these findings suggest that these biomarkers can be used to better define cellular pathways associated with clinical onset and/or severity of acute GVHD and thereby provide potential targets for therapy.
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Pellegrini, Miguel, Guendalina Bergonzoni, Federica Perrone, Ferdinando Squitieri, and Marta Biagioli. "Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington’s Disease." Genes 13, no. 11 (November 3, 2022): 2017. http://dx.doi.org/10.3390/genes13112017.
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Whether as a cause or a symptom, RNA transcription is recurrently altered in pathologic conditions. This is also true for non-coding RNAs, with regulatory functions in a variety of processes such as differentiation, cell identity and metabolism. In line with their increasingly recognized roles in cellular pathways, RNAs are also currently evaluated as possible disease biomarkers. They could be informative not only to follow disease progression and assess treatment efficacy in clinics, but also to aid in the development of new therapeutic approaches. This is especially important for neurological and genetic disorders, where the administration of appropriate treatment during the disease prodromal stage could significantly delay, if not halt, disease progression. In this review we focus on the current status of biomarkers in Huntington’s Disease (HD), a fatal hereditary and degenerative disease condition. First, we revise the sources and type of wet biomarkers currently in use. Then, we explore the feasibility of different RNA types (miRNA, ncRNA, circRNA) as possible biomarker candidates, discussing potential advantages, disadvantages, sources of origin and the ongoing investigations on this topic.
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Lin, Selena Y., Shu-Ching Chang, Stella Lam, Romela Irene Ramos, Kevin Tran, Shuichi Ohe, Matthew P. Salomon, et al. "Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy." Clinical Chemistry 66, no. 1 (December 30, 2019): 169–77. http://dx.doi.org/10.1373/clinchem.2019.307140.
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Abstract BACKGROUND Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel. METHODS Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profiling was performed using 5 known melanoma mRNA biomarkers and BRAF V600E DNA mutation. CTC biomarker status associations with clinical outcomes were assessed. RESULTS CTCs were detected in 88% of blood samples from patients with melanoma. CTC-derived biomarkers and clinical variables analyzed using classification and regression tree analysis revealed that a combination of lactate dehydrogenase, CTC-mRNA biomarkers, and tumor BRAF–mutation status was indicative of clinical outcomes for patients with stage IV melanoma (n = 52). The panel stratified low-risk and high-risk patients, whereby the latter had poor disease-free (P = 0.03) and overall survival (P = 0.02). Incorporation of a DNA biomarker with mRNA profiling increased overall CTC-detection capability by 57% compared to mRNA profiling only. RNA sequencing of isolated CTCs identified significant catenin beta 1 (CTNNB1) overexpression (P <0.01) compared to nondisease donor blood. CTC-CTNNB1 was associated with progressive disease/stable disease compared to complete-responder patient status (P = 0.02). Serial CTC profiling identified subclinical disease in patients who developed progressive disease during treatment/follow-up. CONCLUSIONS CTC-derived mRNA/DNA biomarkers have utility for monitoring CII, targeted, and combinatorial therapies in metastatic melanoma patients.
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Iqbal, Safdar, Abdul Qadeer Saad, Aamal Haleem, Zahida Parveen, Imtiaz Hussain, Muhammad Kashif Qamar, and Muhammad Zahid. "Medically Important Novel Biomarkers Therapy for Targeting the Cancerous and Tumor Cells in Combating the Infectious Diseases." Saudi Journal of Pathology and Microbiology 6, no. 10 (October 27, 2021): 395–400. http://dx.doi.org/10.36348/sjpm.2021.v06i10.013.
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Cancer biomarkers are the biological molecules produced by the body or tumor in a person with cancer. In order to place the functioning of biomarkers for clinical investigating, they are passed through different clinical trials in order to check their treatment rate as compared to the normal markers. Different genes are involved in causing the breast cancer and early diagnosis through biomarkers provides an effective way to control the mutations caused in cancerous tissues. Genetic biomarkers are those biological molecules that can detect the change in the DNA and RNA structures. HER2 somatic mutations lead to increase in progressions of cancer development non-small cell lung cancers as well as in breast cells. The most important biomarkers are ALF-alpha-fetoprotein is a protein that in humans is encoded by the AFP gene in the liver. Mutational defect in AFP gene leads to severe damage to liver. C-reactive protein (CRP) is the biomarker for inflammation in the body cells. Prostate specific antigen (PSA) is the biomarker used for detection of prostate cancer. Microsatellite instability analysis of a tumor which provides predictive and also prognostic information. Cerebrospinal fluid (CSF) is the important biomarker for the diagnosis of dementia, Alzheimer’s disease pathologies.
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Panta, Prashanth, and Venkat Raghavender Venna. "Salivary RNA Signatures in Oral Cancer Detection." Analytical Cellular Pathology 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/450629.
Full textAbstract:
Oral squamous cell carcinomas (OSCC) are common malignancies that affect almost a million people every year. The key issue in reducing mortality and morbidity associated with OSCC is to develop novel strategies to identify OSCC at an early stage. One such strategy is the identification of biomarkers. So far, more than 100 biomarkers are recognized in the detection of oral cancer and they range from proteins to nucleic acids (DNAs, RNAs). Detection of ribose nucleic acids in saliva is a recent trend in diagnosing oral cancer. Studies have shown statistically significant changes in the levels of salivary transcriptomes in patients with oral squamous cell carcinomas. These biomarkers have displayed high sensitivity and specificity. Also, new point-of-care platforms such as oral fluid nanosensor test are now available that will soon emerge as chair-side tools for early detection of oral cancer. The aim of this review is to highlight the importance of salivary transcriptomes in oral cancer detection.
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Nitusca, Diana, Anca Marcu, Alis Dema, Loredana Balacescu, Ovidiu Balacescu, Razvan Bardan, Alin Adrian Cumpanas, et al. "Long Noncoding RNA NEAT1 as a Potential Candidate Biomarker for Prostate Cancer." Life 11, no. 4 (April 6, 2021): 320. http://dx.doi.org/10.3390/life11040320.
Full textAbstract:
Background: Prostate cancer (PCa) remains one of the leading causes of cancer-related mortality in men worldwide, mainly due to unsatisfactory diagnostic methods used at present, which lead to overdiagnosis, unnecessary biopsies and treatment, or misdiagnosis in early asymptomatic stages. New diagnostic biomarkers are needed for a correct and early diagnosis. Long noncoding RNAs (lncRNAs) have been broadly studied for their involvement in PCa biology, as well as for their potential role as diagnostic biomarkers. Methods: We conducted lncRNA profiling in plasma and microdissected formalin-fixed paraffin-embedded (FFPE) tissues of PCa patients and attempted validation for commonly dysregulated individual lncRNAs. Results: Plasma profiling revealed eight dysregulated lncRNAs, while microarray analysis revealed 717 significantly dysregulated lncRNAs, out of which only nuclear-enriched abundant transcript 1 (NEAT1) was commonly upregulated in plasma samples and FFPE tissues. NEAT1’s individual validation revealed statistically significant upregulation (FC = 2.101, p = 0.009). Receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) value of 0.7298 for NEAT1 (95% CI = 0.5812–0.8785), suggesting a relatively high diagnostic value, thus having a potential biomarker role for this malignancy. Conclusions: We present herein data suggesting that NEAT1 could serve as a diagnostic biomarker for PCa. Additional studies of larger cohorts are needed to confirm our findings, as well as the oncogenic mechanism of NEAT1 in the development of PCa.