The expression of cuproptosis-related genes in hepatocellular carcinoma and their relationships with prognosis

Xueying Zhao; Jin Chen; Shangqi Yin; Jingren Shi; Mei Zheng; Chaonan He; Huan Meng; Ying Han; Jinyu Han; Jingjing Guo; Zhengrong Yuan; Yajie Wang

doi:10.3389/fonc.2022.992468

The expression of cuproptosis-related genes in hepatocellular carcinoma and their relationships with prognosis

Front Oncol. 2022 Oct 14:12:992468. doi: 10.3389/fonc.2022.992468. eCollection 2022.

Authors

Xueying Zhao¹, Jin Chen², Shangqi Yin², Jingren Shi², Mei Zheng², Chaonan He², Huan Meng², Ying Han², Jinyu Han², Jingjing Guo², Zhengrong Yuan¹, Yajie Wang²

Affiliations

¹ College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
² Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Abstract

Background: The mechanism of cuproptosis has recently been reported in lipoylated proteins of the tricarboxylic acid (TCA) cycle. Besides, the role of copper was previously recognized in cancer progression. We evaluated the prognostic value of cuproptosis-related gene expression in hepatocellular carcinoma (HCC).

Methods: Remarkable genes were selected both in differential expression analysis and Kaplan-Meier survival analysis from ninety-six cuproptosis-related genes using The Cancer Genome Atlas (TCGA) database. The relationships between clinical characteristics and gene expression were performed with Wilcoxon signed-rank test, Kruskal-Wallis test, and logistic regression. Clinicopathologic factors correlated with overall survival in HCCs conducting univariate and multivariate Cox regression analysis. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Human Protein Atlas (HPA) databases were utilized to verify the results. Furthermore, Gene Set Enrichment Analysis (GSEA) identified the potential key pathways that dominate cuproptosis in HCC.

Results: Elevated ATP7A, SLC25A3, SCO2, COA6, TMEM199, ATP6AP1, LIPT1, DLAT, PDHA1, MTF1, ACP1, FDX2, NUBP2, CIAPIN1, ISCA2 and NDOR1 expression, as well as declined AOC1, FDX1, MT-CO1, and ACO1 expression were significantly emerged in HCC tumor tissues and were significantly associated with HCCs poor survival. The expressions of screened cuproptosis-related genes were prominently related to clinical features. GSEA analysis reported many key signaling pathways (such as natural killer cell mediated cytotoxicity, TCA cycle, glutathione metabolism, ATP-binding cassette (ABC) transporters, Notch signaling pathway, ErbB signaling pathway, and metabolism of xenobiotics by cytochrome p450) were differentially enriched in HCCs with varying degrees of cuproptosis-related genes expression.

Conclusions: The twenty cuproptosis-related genes might be utilized as new candidate prognostic biomarkers for HCC.

Keywords: TCGA; bioinformatics; cuproptosis; hepatocellular carcinoma; prognosis.