Identification and validation of a prognostic four-genes signature for hepatocellular carcinoma: integrated ceRNA network analysis

Hepatol Int. 2019 Sep;13(5):618-630. doi: 10.1007/s12072-019-09962-3. Epub 2019 Jul 18.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, with a poor long-term prognosis worldwide. The functional deregulations of global transcriptome were associated with the genesis and development of HCC, but lacks systematic research and validation.

Methods: A total of 519 postoperative HCC patients were included. We built an interactive and visual competing endogenous RNA network. The prognostic signature was established with the least absolute shrinkage and selection operator algorithm. Multivariate Cox regression analysis was used to screen for independent prognostic factors for HCC overall survival.

Results: In the training set, we identified a four-gene signature (PBK, CBX2, CLSPN, and CPEB3) and effectively predicted the overall survival. The survival times of patients in the high-score group were worse than those in the low-score group (p = 0.0004), and death was also more likely in the high-score group (HR 2.444, p < 0.001). The results were validated in internal validation set (p = 0.0057) and two external validation cohorts (HR 2.467 and 2.6). The signature (AUCs of 1, 2, 3 years were 0.716, 0.726, 0.714, respectively) showed high prognostic accuracy in the complete TCGA cohort.

Conclusions: In conclusion, we successfully built a more extensive ceRNA network for HCC and then identified a four-gene-based signature, enabling prediction of the overall survival of patients with HCC.

Keywords: Competing endogenous RNA; Global transcriptome; Hepatocellular carcinoma; Least absolute shrinkage and selection operator; Overall survival.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes / genetics*
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Polycomb Repressive Complex 1 / genetics
  • Prognosis
  • Proportional Hazards Models
  • RNA / genetics*
  • RNA-Binding Proteins / genetics
  • Real-Time Polymerase Chain Reaction
  • Survival Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • CBX2 protein, human
  • CLSPN protein, human
  • CPEB3 protein, human
  • RNA-Binding Proteins
  • RNA
  • Polycomb Repressive Complex 1
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase