miRNome profiling analysis reveals novel hepatocellular carcinoma diagnostic, prognostic and treatment-related candidate biomarkers: post-hoc analysis of SORAMIC trial.

Abstract

Introduction Early diagnosis of hepatocellular carcinoma as well as evaluation of prognosis and prediction of treatment efficacy remain challenging due to the missing specific non-invasive biomarkers. The aim of this study is to identify disease-specific microRNA (miRNA) patterns for diagnosis, prediction of prognosis and treatment response in patients with hepatocellular carcinoma (HCC). Methods The study population included 42 HCC patients from SORAMIC clinical trial: 22 patients received sorafenib monotherapy, 20 patients underwent 90Y radioembolization in combination with sorafenib. 20 individuals were included in the control group. Hepatocellular carcinoma patients underwent collection of plasma samples before and 7-9 weeks after the beginning of the treatment. Isolation of circulating miRNAs, preparation of small RNA sequencing libraries and next-generation sequencing were performed. Association analysis for novel diagnostic, prognostic and treatment-related candidate biomarkers was performed. Results A total of 42 differentially expressed (16 up-regulated and 26 down-regulated) miRNAs were identified comparing baseline and control group plasma samples. hsa-miR-215-5p and hsa-miR-192-5p were down-regulated, while hsa-miR-483-5p and hsa-miR-23b-3p were up-regulated comparing baseline and 7-9 weeks post-sorafenib monotherapy samples. hsa-miR-215-5p was the sole down-regulated miRNA in the same combination therapy comparison. hsa-miR-183-5p, hsa-miR-28-3p and hsa-miR-1246 were found to be significantly up-regulated comparing non-responders versus responders to sorafenib. High hsa-miR-215-5p expression was significantly associated with worse HCC patients' prognosis. Conclusions Systematic miRNA profiling of highly characterized samples from SORAMIC study revealed a subset of potential miRNA biomarkers for hepatocellular carcinoma diagnosis and prognosis of sorafenib-treated patients' survival.