Low-level expression of microRNA-375 predicts poor prognosis in hepatocellular carcinoma

Tumour Biol. 2016 Feb;37(2):2145-52. doi: 10.1007/s13277-015-3841-0. Epub 2015 Sep 8.

Abstract

MicroRNAs are predicted to play fundamental roles in the tumorigenesis of hepatocellular carcinoma (HCC). MiR-375 is frequently downregulated in HCC and acts as a tumor suppressor by targeting multiple oncogenes. The objective of this study was to evaluate miR-375 expression and its relevance to the prognosis of HCC. MiR-375 expression was measured in cancerous tissues using qRT-PCR and dichotomized based on a median cutoff. The association between miR-375 expression and clinicopathological parameters and prognosis was subsequently determined. Expression levels of miR-375 were detected in a cohort of 38 HCC patients who underwent curative surgery. No significant correlations were observed between miR-375 expression and clinicopathological parameters, such as gender, age, performance status, preoperative serum AFP level, histological grade, HBV-DNA copy number, ascites, cirrhosis, tumor size, number of tumor nodules, and macrovascular invasion. However, miR-375 expression differs across CLIP scores significantly (p < 0.05). A trend toward poorer disease-free survival (DFS) was observed in patients with lower miR-375 expression compared to those with higher miR-375 expression (p = 0.307). Multivariate analysis demonstrated that low miR-375 expression was an independent prognostic predictor for progression (p = 0.032, risk ratio 3.273). Subgroup analysis revealed that low expression of miR-375 was significantly associated with adverse DFS in patients with poorly differentiated histology, higher serum AFP level (≥400 ng/ml), and advanced tumor stage (CLIP score 1∼3) (p = 0.017, 0.009, and 0.024, respectively). Our study demonstrates that miR-375 expression is significantly correlated with DFS and may be a potential prognostic biomarker of disease progression in HCC.

Keywords: Hepatocellular carcinoma; Invasion; MicroRNA-375.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Prognosis
  • Proportional Hazards Models

Substances

  • MIRN375 microRNA, human
  • MicroRNAs