Analysis of cuproptosis in hepatocellular carcinoma using multi-omics reveals a comprehensive HCC landscape and the immune patterns of cuproptosis

• DOI: 10.3389/fonc.2022.1009036
• Publication Date: 2022-11-02T06:34:12Z
• Authors: Xinqiang Li; Peng Jiang; Ruixia Li; Bin Wu; Kai Zhao; Shipeng Li; Jinzhen Cai
• Keywords: 0303 health sciences; 03 medical and health sciences; cell death; single cell RNA analysis; cuproptosis; Oncology; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; HCC; RC254-282; omics; 3. Good health

Cuproptosis represents a novel copper-dependent regulated cell death, distinct from other known cell death processes. In this report, a comprehensive analysis of cuproptosis in hepatocellular carcinoma (HCC) was conducted using multi-omics including genomics, bulk RNA-seq, single cell RNA-seq and proteomics. ATP7A, PDHA1 and DLST comprised the top 3 mutation genes in The Cancer Genome Atlas (TCGA)-LIHC; 9 cuproptosis-related genes showed significant, independent prognostic values. Cuproptosis-related hepatocytes were identified and their function were evaluated in single cell assays. Based on cuproptosis-related gene expressions, two immune patterns were found, with the cuproptosis-C1 subtype identified as a cytotoxic immune pattern, while the cuproptosis-C2 subtype was identified as a regulatory immune pattern. Cuproptosis-C2 was associated with a number of pathways involving tumorigenesis. A prognosis model based on differentially expressed genes (DEGs) of cuproptosis patterns was constructed and validated. We established a cuproptosis index (CPI) and further performed an analysis of its clinical relevance. High CPI values were associated with increased levels of alpha-fetoprotein (AFP) and advanced tumor stages. Taken together, this comprehensive analysis provides important, new insights into cuproptosis mechanisms associated with human HCC.