Identification and validation of a new gene signature predicting prognosis of hepatocellular carcinoma patients by network analysis of stemness indices

Expert Rev Gastroenterol Hepatol. 2021 Jun;15(6):699-709. doi: 10.1080/17474124.2021.1845142. Epub 2021 Feb 22.

Abstract

Background: Stem cells play an important role in hepatocellular carcinoma (HCC). However, their precise effect on HCC tumorigenesis and progression remains unclear. The present study aimed to characterize stem cell-related gene expression in HCC.Methods: The mRNA expression-based stemness index (mRNAsi) was used to analyze the clinical characteristics and prognosis of HCC patients. The weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network of 374 HCC patients. Finally, six genes were used to construct the prognosis signature.Results: HCC patients had a higher mRNAsi score than healthy people, suggesting poor prognosis. Two gene modules highly related to mRNAsi were identified. Multivariate Cox analysis was carried out to establish a Cox proportional risk regression model. The risk score for each patient was the sum of the product of each gene expression and its coefficient. Survival analysis suggested that the low-risk group had a significantly better prognosis.Conclusions: The established six-gene signature was able to predict patient prognosis accurately. This new signature should be verified in prospective studies in order to determine patient prognosis in clinical decision-making.

Keywords: Hepatocellular carcinoma; TCGA; WGCNA; cancer stem cell; mRNAsi.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinogenesis
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Case-Control Studies
  • Clinical Decision Rules*
  • Databases, Factual
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Neoplasm Staging
  • Neoplastic Stem Cells / physiology*
  • Nomograms*
  • RNA, Messenger / metabolism
  • ROC Curve
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • RNA, Messenger