Research Paper Volume 13, Issue 10 pp 13822—13845
Development and validation of epithelial mesenchymal transition-related prognostic model for hepatocellular carcinoma
- 1 Public Research Platform, Department of Radiation Oncology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- 2 School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
- 3 Central Laboratory, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- 4 Department of Radiation Oncology, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
- 5 Department of Infectious Disease, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Linhai 317000, Zhejiang Province, China
Received: November 28, 2020 Accepted: March 27, 2021 Published: April 30, 2021
https://doi.org/10.18632/aging.202976How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Epithelial cell transformation (EMT) plays an important role in the pathogenesis and metastasis of hepatocellular carcinoma (HCC). We aimed to establish a genetic risk model to evaluate HCC prognosis based on the expression levels of EMT-related genes. The data of HCC patients were collected from TCGA and ICGC databases. Gene expression differential analysis, univariate analysis, and lasso combined with stepwise Cox regression were used to construct the prognostic model. Kaplan–Meier curve, receiver operating characteristic (ROC) curve, calibration analysis, Harrell’s concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the predictive ability of the risk model or nomogram. GO and KEGG were used to analyze differently expressed EMT genes, or genes that directly or indirectly interact with the risk-associated genes. A 10-gene signature, including TSC2, ACTA2, SLC2A1, PGF, MYCN, PIK3R1, EOMES, BDNF, ZNF746, and TFDP3, was identified. Kaplan–Meier survival analysis showed a significant prognostic difference between high- and low-risk groups of patients. ROC curve analysis showed that the risk score model could effectively predict the 1-, 3-, and 5-year overall survival rates of patients with HCC. The nomogram showed a stronger predictive effect than clinical indicators. C-index, DCA, and calibration analysis demonstrated that the risk score and nomogram had high accuracy. The single sample gene set enrichment analysis results confirmed significant differences in the types of infiltrating immune cells between patients in the high- and low-risk groups. This study established a new prediction model of risk gene signature for predicting prognosis in patients with HCC, and provides a new molecular tool for the clinical evaluation of HCC prognosis.