Development and Validation of an RNA Binding Protein-associated Prognostic Model for Hepatocellular Carcinoma

J Clin Transl Hepatol. 2021 Oct 28;9(5):635-646. doi: 10.14218/JCTH.2020.00103. Epub 2021 Apr 13.

Abstract

Background and aims: The survival rate of patients with hepatocellular carcinoma is variable. The abnormal expression of RNA-binding proteins (RBPs) is closely related to the occurrence and development of malignant tumors. The primary aim of this study was to identify RBPs related to the prognosis of liver cancer and to construct a prognostic model of liver cancer.

Methods: We downloaded the hepatocellular carcinoma gene sequencing data from The Cancer Genome Atlas (cancergenome.nih.gov/) database, constructed a protein-protein interaction network, and used Cytoscape to realize the visualization. From among 325 abnormally expressed genes for RBPs, 9 (XPO5, enhancer of zeste 2 polycomb repressive complex 2 subunit [EZH2], CSTF2, BRCA1, RRP12, MRPL54, EIF2AK4, PPARGC1A, and SEPSECS) were selected for construction of the prognostic model. Then, we further verified the results through the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo/) database and in vitro experiments.

Results: A prognostic model was constructed, which determined that the survival time of patients in the high-risk group was significantly shorter than that of the low-risk group (p<0.01). Univariate and multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor (p<0.01). We also constructed a nomogram based on the risk score, survival time, and survival status. At the same time, we verified the high expression and cancer-promoting effects of EZH2 in tumors.

Conclusions: Survival, receiver operating characteristic curve and independent prognostic analyses demonstrated that we constructed a good prognostic model, which might be useful for estimating the survival of patients with hepatocellular carcinoma.

Keywords: Hepatocellular carcinoma; Nomogram; Prognostic model; RNA binding protein.