4.6 Article

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

Journal

JOURNAL OF CANCER
Volume 12, Issue 13, Pages 4011-4024

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/jca.51303

Keywords

digestive system cancers; microRNA-10b; prognosis prediction; biomarker

Categories

Funding

  1. Jiangsu young medical talent [QNRC2016859]
  2. Advance Research Program for Young and Middle-aged Backbone of Suzhou Science & Technology Town Hospital [2019Y04]
  3. National Natural Science Foundation of China [82003219]
  4. Suzhou Science and Technology Development Project Jiangsu [SYS2019059]
  5. Scientific Research Program for Young Talents of China National Nuclear Corporation [51003]
  6. Pre-research program of the Second Affiliated Hospital of Soochow University [SDFEYGJ1901, SDFEYBS1701]

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Our study found that abnormal expression of miR-10b in digestive system cancers is associated with poor prognosis, especially in colorectal cancer, gastric cancer, hepatocellular carcinoma, and esophageal carcinoma. Target genes of miR-10b are mainly enriched in pivotal signaling pathways related to tumor progression, such as cell cycle, FoxO, Notch, etc.
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.

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