Potential role of lncRNA-TSIX, miR-548-a-3p, and SOGA1 mRNA in the diagnosis of hepatocellular carcinoma

Mol Biol Rep. 2019 Aug;46(4):4581-4590. doi: 10.1007/s11033-019-04810-x. Epub 2019 Apr 19.

Abstract

Recent trends are moving towards the use of the circulating transcriptome as a potential diagnostic and therapeutic tool for hepatocellular carcinoma (HCC). The aim of this study is to identify circulatory RNA based biomarker panel, in addition to their relationship to the outcome in HCC. First, utilizing bioinformatics tools, we selected an HCC-specific RNA-based biomarker panel that depended on the integration of suppressor of glucose autophagy-associated (SOGA1) gene expression with the chosen panel of epigenetic regulators of this gene [long non-coding RNA antisense for X-inactive-specific transcript (lncRNA-TSIX) and microRNA-548-a-3p (miR-548-a-3p)]. Second, we attempted to validate these biomarkers using the sera of 65 patients with HCC, 34 patients with chronic hepatitis C virus (CHC) infection and 32 healthy volunteers. Finally, the expression levels of the chosen RNA-based biomarker panel were assessed in the serum samples using qRT-PCR assays. The panel of 3 RNA-based biomarkers (lncRNA-TSIX, miR-548-a-3p, and SOGA1) exhibited high sensitivity and specificity in differentiating HCC patients from CHC patients and healthy controls. Among these 3 RNAs, serum lncRNA-TSIX and SOGA1 were independent prognostic factor. The chosen circulatory RNA-based biomarker panel may serve as a diagnostic and prognostic biomarker for HCC.

Keywords: Bioinformatics; Competing endogenous RNA; Diagnosis; Hepatocellular carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Female
  • Hepatitis C, Chronic / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Sensitivity and Specificity

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • MIRN548 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • SOGA1 protein, human
  • TSIX long non-coding RNA, human