Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

PLoS One. 2020 Sep 22;15(9):e0239386. doi: 10.1371/journal.pone.0239386. eCollection 2020.

Abstract

While tumor resection and liver transplantation (LT) represent potentially curative therapeutic options for patients with early-stage hepatocellular carcinoma (HCC), the identification of the ideal surgical candidates has remained challenging. Just recently, miRNA-193a-5p was described as a tumor suppressor in murine and human HCC but only little is known about circulating miRNA-193a-5p in HCC patients. Here, we evaluated serum levels of miR-193a-5p by qPCR in 41 HCC patients undergoing tumor resection (n = 33) or LT (n = 8) and 20 controls. Circulating relative miR-193a-5p levels were significantly elevated in HCC patients compared to healthy controls. While relative miR-193a-5p levels were comparable between patients of different underlying disease etiology and tumor size, high relative miR-193a-5p levels were predictive for the patients' postoperative outcome, which was confirmed in uni- and multivariate Cox-regression analysis. As such, HCC patients with a preoperative relative miR-193a-5p level above the ideal cut-off value (3.57) had a median overall survival (OS) of only 451 days compared to 1158 days in patients with a relative miR-193a-5p level below this cut-off value. Our data support a novel function of miR-193a-5p as a biomarker in early-stage HCC patients that might help to identify the best surgical candidates in terms of postoperative outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Case-Control Studies
  • Female
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplasm Staging
  • Proportional Hazards Models
  • ROC Curve
  • Survival Rate
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MIRN193 microRNA, human
  • MicroRNAs

Grants and funding

Work in the lab of T.L. was funded from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program through the ERC Consolidator Grant PhaseControl (Grant Agreement n° 771083). The lab of T.L. was further supported by the German Cancer Aid (Deutsche Krebshilfe 110043 and a Mildred-Scheel-Professorship), the German-Research-Foundation (SFB-TRR57/P06 and LU 1360/3-1), the Ernst-Jung-Foundation Hamburg, the IZKF (interdisciplinary centre of clinical research) Aachen and a grant from the medical faculty of the RWTH Aachen.