Clinical significance and prognostic role of hypoxia-induced microRNA 382 in gastric adenocarcinoma

PLoS One. 2019 Oct 9;14(10):e0223608. doi: 10.1371/journal.pone.0223608. eCollection 2019.

Abstract

Hypoxia and angiogenesis are critical components in the progression of solid cancer, including gastric cancers (GCs). miR-382 has been identified as a hypoxia-induced miR (hypoxamiR), but the clinical significance in GCs has not been identified yet. To explore the clinical and prognostic importance of miR-382 in GCs, the surgical specimens of 398 patients with GCs in KNU hospital in Korea, the total of 183 patients was randomly selected using simple sampling methods and big data with 446 GCs and 45 normal tissues from the data portal (https://portal.gdc.cancer.gov/) were analysed. Expression of miR-382 as well as miR-210, as a positive control hypoxamiR by qRT-PCR in histologically malignant region of GCs showed significantly positive correlation (R = 0.516, p<0.001). High miR-210 and miR-382 expression was significantly correlated with unfavorable prognosis including advanced GCs (AGC), higher T category, N category, pathologic TNM stage, lymphovascular invasion, venous invasion, and perinueral invasion, respectively (all p<0.05). In univariate analysis, high miR-210 expression was significantly associated with worse overall survival (OS) (p = 0.036) but not high miR-382. In paired 60 gastric normal and cancer tissues, miR-382 expression in cancer tissues was significantly higher than normal counterpart (p = 0.003), but not miR-210 expression. However, by increasing the patient number from the big data analysis, miR-210 as well as miR-382 expression in tumor tissues was significantly higher than the normal tissues. Our results suggest that miR-382, as novel hypoxamiR, can be a prognostic marker for advanced GCs and might be correlated with metastatic potential. miR-382 might play important roles in the aggressiveness, progression and prognosis of GCs. In addition, miR-382 give a predictive marker for progression of GCs compared to the normal or preneoplastic lesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Biomarkers, Tumor / standards
  • Cell Hypoxia
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • MicroRNAs / standards
  • Middle Aged
  • Sensitivity and Specificity
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • MIRN382 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by the National Research Foundation (NRF) grant funded by the Korean government (MSIP) (NRF-2012R1A4A1028835 and NRF-2017R1A2B3002227) to Y.M.L. as a PI. These funders have no role for this study design, data collection and analysis, decision to publish, or preparation of the manuscript.