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

Autor(es):Mostrar menos -

Pewarchuk, Michelle E. ^[1] ; Barros-Filho, Mateus C. ^{[1, 2]} ; Minatel, Brenda C. ^[1] ; Cohn, David E. ^[1] ; Guisier, Florian ^{[1, 3, 4, 5]} ; Sage, Adam P. ^[1] ; Marshall, Erin A. ^[1] ; Stewart, Greg L. ^[1] ; Rock, Leigha D. ^{[1, 6]} ; Garnis, Cathie ^{[1, 7]} ; Lam, Wan L. ^[1]

Afiliação do(s) autor(es)

^[1] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3 - Canada

^[2] ACCamargo Canc Ctr, Int Res Ctr, BR-01508010 Sao Paulo, SP - Brazil

^[3] Rouen Univ Hosp, Dept Pulmonol, Thorac Oncol & Resp Intens Care, F-76000 Rouen - France

^[4] Rouen Univ Hosp, INSERM 1404, CRB, CIC, F-76000 Rouen - France

^[5] Univ Rouen, IRIB, EA 4108, QuantIF, LITIS, F-76000 Rouen - France

^[6] Dalhousie Univ, Fac Dent, Halifax, NS B3H 4R2 - Canada

^[7] Univ British Columbia, Div Otolaryngol, Dept Surg, Vancouver, BC V5Z 1L3 - Canada

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 22 NOV 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 18/06138-8 - Pequenos RNAs não codificadores como reguladores chave no câncer de tireóide
• Beneficiário: Mateus de Camargo Barros Filho
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado