The correlation of circulating pro-angiogenic miRNAs' expressions with disease risk, clinicopathological features, and survival profiles in gastric cancer

Cancer Med. 2018 Aug;7(8):3773-3791. doi: 10.1002/cam4.1618. Epub 2018 Jul 12.

Abstract

This study aimed to explore the correlation of circulating pro-angiogenic miRNAs' expressions with risk, clinicopathological features, and survival profiles in gastric cancer (GC). Three hundred and thirty-three GC patients underwent radical resection and 117 health controls (HCs) were recruited for this study. Plasma samples were obtained from GC patients before the operation and from HCs after enrollment. Fourteen pro-angiogenic miRNAs were asseassed by quantitative polymerase chain reaction (qPCR). Disease-free survival (DFS) and overall survival (OS) of GC patients were calculated and the median follow-up duration was 36.0 months. Seven out of 14 pro-angiogenic miRNAs including let-7f, miR-17-5p, miR-18a, miR-19b-1, miR-20a, miR-210, and miR-296 were observed to be elevated in GC patients compared with HCs. MiR-18a, miR-20a, and miR-210 disclosed good predictive values of GC risk. Six pro-angiogenic miRNAs including miR-17-5p, miR-92a, miR-210, miR-20a, miR-18a, and miR-296 expressions were positively while 1 pro-angiogenic miRNA (miR-130a) was negatively correlated with tumor malignancy degree in GC patients. K-M curve disclosed that 5 pro-angiogenic miRNAs including miR-17-5p, miR-18a, miR-20a, miR-92a, and miR-210 correlated with worse DFS, while 4 pro-angiogenic miRNAs including miR-17-5p, miR-18a, miR-20a, and miR-210 associated with shorter OS. Further multivariate Cox's analysis revealed that miR-17-5p, miR-18a, miR-20a, and miR-210 were independent predictive factors for unfavorable DFS and OS. In conclusion, circulating pro-angiogenic miRNAs could serve as novel noninvasive biomarkers for disease risk and malignancy degree, and miR-17-5p, miR-18a, miR-20a, and miR-210 are independent factors predicting poor prognosis in GC patients.

Keywords: circulating; gastric cancer; miRNA; pro-angiogenic; prognosis.

MeSH terms

  • Aged
  • Biomarkers, Tumor*
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics*
  • Combined Modality Therapy
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / genetics*
  • Prognosis
  • ROC Curve
  • Risk Assessment
  • Risk Factors
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MicroRNAs