Identification of a prognostic signature of nine metabolism-related genes for hepatocellular carcinoma

Chaozhi Tang; Jiakang Ma; Xiuli Liu; Zhengchun Liu

doi:10.7717/peerj.9774

Identification of a prognostic signature of nine metabolism-related genes for hepatocellular carcinoma

PeerJ. 2020 Sep 1:8:e9774. doi: 10.7717/peerj.9774. eCollection 2020.

Authors

Chaozhi Tang^#¹, Jiakang Ma^#², Xiuli Liu³, Zhengchun Liu⁴

Affiliations

¹ Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
² Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Department of Oncology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
⁴ Department of Radiation Oncology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.

^# Contributed equally.

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer. Since changes in liver metabolism contribute to liver disease development, it is necessary to build a metabolism-related prognostic model for HCC.

Methods: We constructed a metabolism-related-gene (MRG) signature comprising nine genes, which segregated HCC patients into high- and low-risk groups.

Results: The survival rate (overall survival: OS; relapse-free survival; and progression-free survival) of patients in the low-risk group of The Cancer Genome Atlas (TCGA) cohort was significantly higher than that of patients in the high-risk group. The OS prognostic signature was validated in the International Cancer Genome Consortium independent cohort. The corresponding receiver operating characteristic curves of the model indicated that the signature had good diagnostic efficiency, in terms of improving OS over 1, 3, and 5 years. Hierarchical analysis demonstrated that the MRG signature was significantly associated with better prognosis in male patients, patients aged ≤ 65 years, and patients carrying the wild-type TP53 or CTNNB1 genes. A nomogram was established, and good performance and clinical practicability were confirmed. Additionally, using the GSE109211 dataset from the Gene Expression Omnibus database, we were able to verify that the nine genes in this MRG signature had different responses to sorafenib, suggesting that some of these MRGs may act as therapeutic targets for HCC.

Conclusions: We believe that these findings will add value in terms of the diagnosis, treatment, and prognosis of HCC.

Keywords: Gene Expression Omnibus; Hepatocellular carcinoma; Metabolism-related genes; Prognostic signature; The Cancer Genome Atlas.

Grants and funding

This work was supported by the National Natural Science Foundation of China (2016GXNSFAA380306) and the self-generated project of the Guangxi Zhuang Autonomous Region Health Department (Z20170816), China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.