Construction of a long non-coding RNA-associated ceRNA network reveals potential prognostic lncRNA biomarkers in hepatocellular carcinoma

Pathol Res Pract. 2018 Dec;214(12):2031-2038. doi: 10.1016/j.prp.2018.09.022. Epub 2018 Sep 27.

Abstract

Objectives: Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related mortality in the world. Accumulating evidence has highlighted the regulatory roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in HCC.

Methods: The lncRNA expression data and corresponding patient information were obtained from The Cancer Genome Atlas (TCGA) database. Competing lncRNA-mRNA interactions were identified using the hypergeometric test. Co-expression analysis was implemented using the Spearman correlation coefficient. Multivariate Cox regression survival analysis was utilized to extract prognostic lncRNAs in the network.

Results: Based on the "ceRNA hypothesis", a global lncRNA-associated ceRNA network (LCeNET) in HCC was constructed. Nine lncRNAs were identified as hubs and found to be enriched in various cancer-related biological processes. In addition, ceRNA pairs associated with survival were screened to construct a lncRNA-miRNA-mRNA sub network. Finally, we developed a sixteen-lncRNA model that could classify patients into high- and low-risk subgroups with different survival outcomes, and MCM3AP-AS1 functioned as a hub in both LCeNET and prognostic model.

Conclusions: Our work will improve the understanding of lncRNA-mediated ceRNA regulatory mechanisms in HCC pathogenesis and facilitate the identification of candidate prognostic biomarkers for HCC.

Keywords: Competitive endogenous RNA; Liver hepatocellular carcinoma; Long non-coding RNAs; Prognostic biomarker.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding