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Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery

1
Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada
2
International Research Center, A.C.Camargo Cancer Center, Sao Paulo 01508-010, Brazil
3
Department of Pulmonology, Thoracic Oncology and Respiratory Intensive Care & CIC-CRB INSERM 1404, Rouen University Hospital, 76000 Rouen, France
4
QuantIF-LITIS EA 4108, IRIB, Rouen University, 76000 Rouen, France
5
Faculty of Dentistry, Dalhousie University, Halifax, NS B3H 4R2, Canada
6
Department of Surgery, Division of Otolaryngology, University of British Columbia, Vancouver, BC V5Z 1L3, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(22), 5697; https://doi.org/10.3390/ijms20225697
Received: 1 September 2019 / Revised: 4 November 2019 / Accepted: 5 November 2019 / Published: 14 November 2019
(This article belongs to the Special Issue Computational Models in Non-Coding RNA and Human Disease)
Recent studies have uncovered microRNAs (miRNAs) that have been overlooked in early genomic explorations, which show remarkable tissue- and context-specific expression. Here, we aim to identify and characterize previously unannotated miRNAs expressed in gastric adenocarcinoma (GA). Raw small RNA-sequencing data were analyzed using the miRMaster platform to predict and quantify previously unannotated miRNAs. A discovery cohort of 475 gastric samples (434 GA and 41 adjacent nonmalignant samples), collected by The Cancer Genome Atlas (TCGA), were evaluated. Candidate miRNAs were similarly assessed in an independent cohort of 25 gastric samples. We discovered 170 previously unannotated miRNA candidates expressed in gastric tissues. The expression of these novel miRNAs was highly specific to the gastric samples, 143 of which were significantly deregulated between tumor and nonmalignant contexts (p-adjusted < 0.05; fold change > 1.5). Multivariate survival analyses showed that the combined expression of one previously annotated miRNA and two novel miRNA candidates was significantly predictive of patient outcome. Further, the expression of these three miRNAs was able to stratify patients into three distinct prognostic groups (p = 0.00003). These novel miRNAs were also present in the independent cohort (43 sequences detected in both cohorts). Our findings uncover novel miRNA transcripts in gastric tissues that may have implications in the biology and management of gastric adenocarcinoma. View Full-Text
Keywords: gastric cancer; novel microRNAs; prognostic factors; noncoding RNAs gastric cancer; novel microRNAs; prognostic factors; noncoding RNAs
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MDPI and ACS Style

Pewarchuk, M.E.; Barros-Filho, M.C.; Minatel, B.C.; Cohn, D.E.; Guisier, F.; Sage, A.P.; Marshall, E.A.; Stewart, G.L.; Rock, L.D.; Garnis, C.; Lam, W.L. Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery. Int. J. Mol. Sci. 2019, 20, 5697. https://doi.org/10.3390/ijms20225697

AMA Style

Pewarchuk ME, Barros-Filho MC, Minatel BC, Cohn DE, Guisier F, Sage AP, Marshall EA, Stewart GL, Rock LD, Garnis C, Lam WL. Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery. International Journal of Molecular Sciences. 2019; 20(22):5697. https://doi.org/10.3390/ijms20225697

Chicago/Turabian Style

Pewarchuk, Michelle E., Mateus C. Barros-Filho, Brenda C. Minatel, David E. Cohn, Florian Guisier, Adam P. Sage, Erin A. Marshall, Greg L. Stewart, Leigha D. Rock, Cathie Garnis, and Wan L. Lam 2019. "Upgrading the Repertoire of miRNAs in Gastric Adenocarcinoma to Provide a New Resource for Biomarker Discovery" International Journal of Molecular Sciences 20, no. 22: 5697. https://doi.org/10.3390/ijms20225697

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