Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma

Fengjiao He; Puhua Zeng; Sijing Ma; Ximing Yang; Huan Liu; Qiong Liu; Yangying Zhou; Hong Zhu

doi:10.3389/fphar.2023.1088993

Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma

Front Pharmacol. 2023 Feb 9:14:1088993. doi: 10.3389/fphar.2023.1088993. eCollection 2023.

Authors

Fengjiao He^{1

2

3}, Puhua Zeng³, Sijing Ma³, Ximing Yang⁴, Huan Liu^{1

2}, Qiong Liu^{1

2}, Yangying Zhou^{1

2}, Hong Zhu^{1

2}

Affiliations

¹ Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, China.
⁴ Medical School, Hunan University of Chinese Medicine, Changsha, China.

Abstract

Background: Cuproptosis is a novel type of regulated cell death and is reported to promote tumor occurrence and progression. However, whether a cuproptosis-related signature has an impact on hepatocellular carcinoma (HCC) is still unclear. Materials and methods: We analyzed the transcriptome data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, and searched for tumor types with different cuproptosis patterns through consistent clustering of cuproptosis genes. We then constructed a Cuproptosis-Related Genes (CRGs)-based risk signature through LASSO COX regression, and further analyzed its impact on the prognosis, clinical characteristics, immune cell infiltration, and drug sensitivity of HCC. Results: We identified the expression changes of 10 cuproptosis-related genes in HCC, and all the patients can be divided into two subtypes with different prognosis by applying the consensus clustering algorithm. We then constructed a cuproptosis-related risk signature and identified five CRGs, which were highly correlated with prognosis and representative of this gene set, namely G6PD, PRR11, KIF20A, EZH2, and CDCA8. Patients in the low CRGs signature group had a favorable prognosis. We further validated the CRGs signature in ICGC cohorts and got consistent results. Besides, we also discovered that the CRGs signature was significantly associated with a variety of clinical characteristics, different immune landscapes and drug sensitivity. Moreover, we explored that the high CRGs signature group was more sensitive to immunotherapy. Conclusion: Our integrative analysis demonstrated the potential molecular signature and clinical applications of CRGs in HCC. The model based on CRGs can precisely predict the survival outcomes of HCC, and help better guide risk stratification and treatment strategy for HCC patients.

Keywords: cuproptosis-related genes; drug sensitivity; hepatocellular carcinoma; prognosis model; tumor microenvironment.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81803787, 82203353), the Fellowship of China Postdoctoral Science Foundation (2022M723565), the Natural Science Foundation of Hunan Province (2022JJ40851), the Health Commission Foundation of Hunan Province (202202085327), and the Traditional Chinese Medicine Administration Foundation of Hunan Province (2021069).