Comprehensive multiomics analysis of cuproptosis-related gene characteristics in hepatocellular carcinoma

Jie Fu; Sixue Wang; Zhenghao Li; Wei Qin; Qing Tong; Chun Liu; Zicheng Wang; Zhiqiang Liu; Xundi Xu

doi:10.3389/fgene.2022.942387

Comprehensive multiomics analysis of cuproptosis-related gene characteristics in hepatocellular carcinoma

Front Genet. 2022 Sep 6:13:942387. doi: 10.3389/fgene.2022.942387. eCollection 2022.

Authors

Jie Fu¹, Sixue Wang², Zhenghao Li¹, Wei Qin¹, Qing Tong¹, Chun Liu¹, Zicheng Wang¹, Zhiqiang Liu¹, Xundi Xu^{1

3}

Affiliations

¹ Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
² Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.
³ Department of General Surgery, South China Hospital of Shenzhen University, Shenzhen, China.

Abstract

Background: The mechanism of copper-induced cell death, which is called cuproptosis, has recently been clarified. However, the integrated role of cuproptosis-related genes in hepatocellular carcinoma (HCC) and its relationship with immune characteristics are still completely unknown. Methods: In this study, the expression, genetic, and transcriptional regulation states of 16 cuproptosis-related genes in HCC were systematically investigated. An unsupervised clustering method was used to identify distinct expression patterns in 370 HCC patients from the TCGA-HCC cohort. Differences in functional characteristics among different expression clusters were clarified by gene set variation analysis (GSVA). The abundances of immune cells in each HCC sample were calculated by the CIBERSORT algorithm. Next, a cuproptosis-related risk score was established based on the significant differentially expressed genes (DEGs) among different expression clusters. Results: A specific cluster of HCC patients with poor prognosis, an inhibitory immune microenvironment, and high expression levels of immune checkpoint molecules was identified based on the expression of the 16 cuproptosis-related genes. This cluster of patients could be well-identified by a cuproptosis-related risk score system. The prognostic value of this risk score was validated in the training and two validation cohorts (TCGA-HCC, China-HCC, and Japan-HCC cohorts). Moreover, the overall expression status of the cuproptosis-related genes and the genes used to establish the cuproptosis-related risk score in specific cell types of the tumor microenvironment were preliminarily clarified by single-cell RNA (scRNA) sequencing data. Conclusion: These results indicated that cuproptosis-related genes play an important role in HCC, and targeting these genes may ameliorate the inhibitory immune microenvironment to improve the efficacy of immunotherapy with immune checkpoint inhibitors (ICIs).

Keywords: cuproptosis-related genes; hepatocellular carcinoma; immune characteristics; multiomics data; risk score; single-cell.