miRNome Profiling Analysis Reveals Novel Hepatocellular Carcinoma Diagnostic, Prognostic and Treatment-Related Candidate Biomarkers: Post hoc Analysis of SORAMIC Trial

Dig Dis. 2024;42(4):336-348. doi: 10.1159/000538757. Epub 2024 Apr 24.

Abstract

Introduction: Early diagnosis of hepatocellular carcinoma (HCC) as well as evaluation of prognosis and prediction of treatment efficacy remains challenging due to the missing specific non-invasive biomarkers. The aim of this study was to identify disease-specific microRNA (miRNA) patterns for diagnosis, prediction of prognosis, and treatment response in patients with 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. HCC 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 HCC diagnosis and prognosis of sorafenib-treated patients' survival.

Keywords: Hepatocellular carcinoma; Micro RNA; Selective internal radiation therapy; Sorafenib.

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Female
  • Gene Expression Profiling
  • Humans
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Male
  • MicroRNAs* / blood
  • MicroRNAs* / genetics
  • Middle Aged
  • Prognosis
  • Sorafenib* / therapeutic use

Substances

  • Biomarkers, Tumor
  • Sorafenib
  • MicroRNAs
  • Antineoplastic Agents