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

Sven H Loosen,Jan Bednarsch,Tom Luedde,Patrick H Alizai,Pia Paffenholz,Christoph Roderburg,Christiane Koppe,Anjali A Roeth,Mihael Vucur,Frank Tacke,Mirco Castoldi,Ulf P Neumann,Sanchari Roy,Theresa H Wirtz,Münevver Demir,Tom F Ulmer,Christian Trautwein,Anne T Schneider,Matias A Avila

doi:10.1371/journal.pone.0239386

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.

Highlights

Hepatocellular carcinoma (HCC) represents the most common primary liver cancer and is associated with rising incidence rates [1]
By reducing levels of nucleolar and spindle-associated protein 1 (NUSAP-1), miR-193a-5p prevented the development of HCC and lower expression of miR-193a-5p was directly associated with shorter survival times of patients
A total of n = 41 early stage HCC patients either receiving tumor resection (n = 33) or liver transplantation (LT, n = 8) were included into this exploratory analysis

Summary

Introduction

Hepatocellular carcinoma (HCC) represents the most common primary liver cancer and is associated with rising incidence rates [1]. By reducing levels of nucleolar and spindle-associated protein 1 (NUSAP-1), miR-193a-5p prevented the development of HCC and lower expression of miR-193a-5p was directly associated with shorter survival times of patients Besides their function as intracellular regulators of gene expression, miRNAs are increasingly used as blood-based biomarkers for manifold biological processes. The use of these miRNAs in clinical routine was hampered by a tremendous lack in data standardization, reproducibility as well as a lack of biological rationale explaining the observed regulation of certain miRNAs. Based on the compelling functional data on miR-193a-5p in human and murine HCC [9], we performed an exploratory analysis, aiming at evaluating a diagnostic and/or prognostic role of circulating miR-193a-5p in a cohort of HCC patients undergoing liver resection or LT for early stage disease

Study design and patient characteristics

Results

Discussion