The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma

Cancer Sci. 2019 Sep;110(9):2905-2923. doi: 10.1111/cas.14138. Epub 2019 Aug 7.

Abstract

The aim of the present study is to construct a competitive endogenous RNA (ceRNA) regulatory network by using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with hepatocellular carcinoma (HCC), and to construct a prognostic model for predicting overall survival (OS) of HCC patients. Differentially expressed lncRNAs, miRNAs, and mRNAs were explored between HCC tissues and normal liver tissues. A prognostic model was built for predicting OS of HCC patients and receiver operating characteristic curves were used to evaluate the performance of the prognostic model. There were 455 differentially expressed lncRNAs, 181 differentially expressed miRNAs, and 5035 differentially expressed mRNAs. A ceRNA regulatory network was constructed based on 43 lncRNAs, 37 miRNAs, and 105 mRNAs. Eight mRNA biomarkers (H2AFX, SQSTM1, ITM2A, PFKP, TPD52L1, ACSL4, STRN3, and CPEB3) were identified as independent risk factors by multivariate Cox regression and were used to develop a prognostic model for OS. The C-indexes in the model group were 0.776 (95% confidence interval [CI], 0.730-0.822), 0.745 (95% CI, 0.699-0.791), and 0.789 (95% CI, 0.743-0.835) for 1-, 3-, and 5-year OS, respectively. The current study revealed potential molecular biological regulation pathways and prognostic biomarkers by the ceRNA regulatory network. A prognostic model based on prognostic mRNAs in the ceRNA network might be helpful to predict the individual mortality risk for HCC patients. The individual mortality risk calculator can be used by visiting the following URL: https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/.

Keywords: competitive endogenous RNA; hepatocellular carcinoma; mRNA; overall survival; prognostic model.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Datasets as Topic
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Liver / pathology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Nomograms
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger