Circulating MicroRNAs in Gastrointestinal Cancer.
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ABSTRACT:
SUBMITTER: Ohtsuka M
PROVIDER: S-EPMC8267753 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMetastasis is the most frequent type of recurrence in gastrointestinal (GI) cancers, and there is an emerging potential for new diagnostic and therapeutic approaches, especially in the cases of metastatic GI carcinomas. The expression profiles of circulating exosomal microRNAs are of particular interest as novel non-invasive diagnostic and prognostic biomarkers for improved detection of GI cancers in body fluids, especially in the serum of patients with recurrent cancers. The aim of this study is to systematically review primary studies and identify the miRNA profiles of serum exosomes of GI cancers.Methods and designThis systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidance. Relevant studies will be identified through a comprehensive search of the following main electronic databases: PubMed, Web of Science, Embase, Scopus, and Google Scholar, with no language restrictions (up to July 2017). Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against pre-defined criteria. The quality assessment of the included studies will be performed by the Newcastle-Ottawa Scale (NOS). Data will be analyzed using Stata software V.12. Publication bias will be assessed by funnel plots, Beggs' and Eggers' tests. The levels of evidence for primary outcomes will be evaluated using the GRADE criteria.DiscussionThe analysis of circulating exosomal miRNA profiles provides attractive screening and non-invasive diagnostic tools for the majority of solid tumors including GI cancers. There is limited information regarding the relationship between serum exosomal miRNA profiles and the pathological condition of patients with different GI cancers. Since there is no specific biomarker for GI cancers, we aim to suggest a number of circulating exosomal miRNA candidates as potential multifaceted GI cancer biomarkers for clinical utility.Systematic review registrationPROSPERO CRD42017057129.
| S-EPMC5693515 | biostudies-literature
Project description:MicroRNAs (miRNAs) are endogenous non-coding small RNA molecules that can be secreted into the circulation and exist in remarkably stable forms. Like intercellular miRNAs, circulating miRNAs participate in numerous regulations of biological process and expressed aberrantly under abnormal or pathological status. The quality and quantity changes of circulating miRNAs are associated with the initiation and progression of cancer and can be easily detected by basic molecular biology techniques. Consequently, considerable effort has been devoted to identify suitable extracellular miRNAs for noninvasive biomarkers in cancer. However, several challenges need to be overcome before the practical application. In this review, we discuss several issues of circulating miRNAs: biological function and basic transport carriers; extracellular cell communication process; roles as reliable cancer biomarkers and usage in targeted cancer therapy; and challenges for clinical application.
| S-EPMC6656856 | biostudies-literature
Project description:Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. Despite numerous advances in therapeutic approaches, this cancer has a poor prognosis when it is diagnosed at late stages. Therefore, the scientific effort is nowadays directed towards the development of new non-invasive and dynamic biomarkers to improve the survival expectancy of CRC patients. In this sense, deregulated expression of many miRNAs has been shown to play an important role for CRC carcinogenesis and dissemination. Noticeably, an increasing number of studies highlight that circulating miRNAs, including those traveling inside exosomes or those released by tumor cells into circulation, constitute a promising tool for early detection, prognosis and therapy selection of CRC. Therefore, in this review we focus on the clinical potential of blood circulating miRNAs as emerging biomarkers with high value to improve the clinical management of CRC patients, providing a deep and complete perspective of the realities and challenges to translate these biomarkers to the clinical context.
| S-EPMC6679000 | biostudies-literature
Project description:PurposeExosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined.Experimental designMicroarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients.ResultsThe serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis.ConclusionExosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.
| S-EPMC3976275 | biostudies-literature
Project description:Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
| S-EPMC2492472 | biostudies-other
Project description:BACKGROUND:We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. METHODOLOGY/PRINCIPAL FINDINGS:TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%. CONCLUSIONS:These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening.
| S-EPMC3536802 | biostudies-literature
Project description:BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for prostate cancer. Here, we investigated the potential of these molecules to assist in prognosis and treatment decision-making. METHODS: MicroRNAs in the serum of patients who had experienced rapid biochemical recurrence (BCR) (n=8) or no recurrence (n=8) following radical prostatectomy (RP) were profiled using high-throughput qRT-PCR. Recurrence-associated miRNAs were subsequently quantitated by qRT-PCR in a validation cohort comprised of 70 patients with Gleason 7 cancers treated by RP, 31 of whom had undergone disease progression following surgery. The expression of recurrence-associated miRNAs was also examined in tumour tissue cohorts. RESULTS: Three miRNAs - miR-141, miR-146b-3p and miR-194 - were elevated in patients who subsequently experienced BCR in the screening study. MiR-146b-3p and miR-194 were also associated with disease progression in the validation cohort, as determined by log-rank tests and Cox proportional hazards regression. Multivariate analysis revealed that miR-146b-3p possessed prognostic information beyond standard clinicopathological parameters. Analysis of tissue cohorts revealed that miR-194 was robustly expressed in the prostate, elevated in metastases, and its expression in primary tumours was associated with a poor prognosis. CONCLUSION: Our study suggests that circulating miRNAs, measured at the time of RP, could be combined with current prognostic tools to predict future disease progression in men with intermediate risk prostate cancers.
| S-EPMC3738112 | biostudies-literature
Project description:Exosomal miRNAs (EmiRs) can be used for prediction of gastric cancer (GC) development. Supposedly, both plasma and urinary microRNAs can also be potential biomarkers for screening, but the diagnostic values of EmiRs in blood and urine are not fully studied. We here collected both types of samples from GC patients and healthy individuals and conducted miRNA sequencing to identify key members of EmiRs in GC. The exosomes samples derived from blood and urine were collected from 3 healthy individuals and 7 GC patients. Differentially expressed miRNAs (DEmiRNAs) were acquired, ontology enrichment analysis and Protein-protein Interaction (PPI) enrichment analysis were performed. There were 8 DEmiRNAs in the serum and 3 DEmiRNAs in the urine. For GC patients, there were three up-regulated DEmiRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) in the serum exosomes, and one up-regulated DEmiRNA (hsa-miR-1246) in the urinary exosomes. Using miRNA target prediction databases, we found 418 common targets of hsa-miR-15b-3p, 35 common targets of hsa-miR-151a-3p, 117 common targets of hsa-miR-130b-3p, and 357 common targets of hsa-miR-1246. Some commonly enriched ontology terms were found, including GO BP terms like cell surface receptor signaling pathway involved in cell-cell signaling, positive regulation of catabolic process, morphogenesis of an epithelium, and GO CC terms perinuclear region of cytoplasm. The PPI network show some key nodes, including TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1. Together, this study provided an integrative analysis of expression profile of key circulating exosomal microRNAs. Four key exosomal miRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) and the interaction network or enrichments based on their targets (TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1) may provide a reference of the molecular mechanisms in the GC development.
| S-EPMC8323470 | biostudies-literature
Project description:MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been previously reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. The pre-treatment sera of 42 stage II–III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs.
| S-ECPF-GEOD-49035 | biostudies-other
Project description:MicroRNAs are small noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular messenger RNAs. They are frequently dysregulated in cancer and have shown great potential as tissue-based markers for cancer classification and prognostication. microRNAs are also present in extracellular human body fluids such as serum, plasma, saliva, and urine. Most of circulating microRNAs are present in human plasma and serum cofractionate with the Argonaute2 (Ago2) protein. However, circulating microRNAs have been also found in membrane-bound vesicles such as exosomes. Since microRNAs circulate in the bloodstream in a highly stable, extracellular form, they may be used as blood-based biomarkers for cancer and other diseases. A knowledge base of extracellular circulating miRNAs is a fundamental tool for biomedical research. In this work, we present miRandola, a comprehensive manually curated classification of extracellular circulating miRNAs. miRandola is connected to miRò, the miRNA knowledge base, allowing users to infer the potential biological functions of circulating miRNAs and their connections with phenotypes. The miRandola database contains 2132 entries, with 581 unique mature miRNAs and 21 types of samples. miRNAs are classified into four categories, based on their extracellular form: miRNA-Ago2 (173 entries), miRNA-exosome (856 entries), miRNA-HDL (20 entries) and miRNA-circulating (1083 entries). miRandola is available online at: http://atlas.dmi.unict.it/mirandola/index.html.
| S-EPMC3477145 | biostudies-other