Comprehensive evaluation of microRNA-10b in digestive system cancers reveals prognostic implication and signaling pathways associated with tumor progression

J Cancer. 2021 May 13;12(13):4011-4024. doi: 10.7150/jca.51303. eCollection 2021.

Abstract

Background: Digestive system cancers (DSCs) have been recognized to be linked with high morbidity and mortality. Recent studies have reported that microRNA-10b (miR-10b) is abnormally expressed in DSCs and associated with prognosis. However, the inconclusive results and unknown underlying mechanisms promoted us to perform this study. Methods: We systematic searched several databases for eligible studies and conducted quantitative analysis for evidence regarding the associations between miR-10b and survival outcome of DSCs. We also performed a series of bioinformatics analyses to uncover the potential mechanisms. Results: A total of 32 eligible studies with 3392 patients were included. Increased miR-10b expression was linked with unfavorable overall survival (OS) in DSCs (HR=1.72; 95% CI: 1.30-2.27; P <0.001). When stratified by tumor type, the impact of miR-10b overexpression on poor prognosis was observed in colorectal cancer, gastric cancer, hepatocellular carcinoma, and esophageal carcinoma, but not in pancreatic cancer. Subsequently, we predicted the targets of miR-10b and conducted functional enrichment analyses. The results disclosed that miR-10b targets were predominantly enriched in some vital biological terms and pivotal signaling pathways associated with tumor progression including cell cycle, FoxO, proteoglycans, central carbon metabolism, p53, Notch, HIF-1, focal adhesion, AMPK, and pancreatic cancer. Moreover, a protein-protein interaction (PPI) network was also constructed to identify the top ten hub genes and significant modules and demonstrated the underlying interactions among them. Conclusion: Our results indicated that miR-10b could act as a significant biomarker in the prognosis DSCs. However, more research should be performed to test these findings.

Keywords: biomarker; digestive system cancers; microRNA-10b; prognosis prediction.