Transcriptomic Analyses Reveal Long Non-Coding RNA in Peripheral Blood Mononuclear Cells as a Novel Biomarker for Diagnosis and Prognosis of Hepatocellular Carcinoma

Int J Mol Sci. 2022 Jul 17;23(14):7882. doi: 10.3390/ijms23147882.

Abstract

Novel biomarkers are highly required for the diagnosis and predicting prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the profiles of long non-coding RNAs (lncRNAs) obtained from the peripheral blood mononuclear cells (PBMCs) of patients with HCC and PBMCs from a co-culture model using transcriptomic analysis. The differentially expressed lncRNAs (DElncRNAs) were then characterized and integrated as cancer-induced lncRNAs. Among them, three up-regulating DElncRNAs including MIR4435-2HG, SNHG9 and lnc-LCP2-1 and one down-regulating, lnc-POLD3-2, were identified. The functional analysis showed that these enriched lncRNAs were mainly associated with carcinogenesis and immune responses. Following further validation in PBMCs samples (100 HBV-related HCC, 100 chronic hepatitis B and 100 healthy controls), MIR4435-2HG, lnc-POLD3-2 and their combination were revealed to be sensitive biomarkers in discriminating HCC from non-HCC (AUROC = 0.78, 0.80, and 0.87, respectively), particularly among individuals with normal serum alpha-fetoprotein levels. Additionally, high circulating SNHG9 expression was shown to be an independent prognostic factor of overall survival in patients with HCC. These results indicate that determining these lncRNAs in PBMCs could serve as novel diagnostic and prognostic biomarkers for HBV-related HCC.

Keywords: alpha-fetoprotein; biomarker; hepatocellular carcinoma; long non-coding RNA; peripheral blood mononuclear cells; transcriptomic profile.

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • RNA, Long Noncoding* / metabolism
  • Transcriptome

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • RNA, Long Noncoding

Grants and funding

This research was supported by the Thailand Research Fund (RTA6280004), the Second Century Fund (C2F), Chulalongkorn University, National Institute of General Medical Sciences of the National Institutes of Health [P20GM125503 to I.N.], and Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.