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

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.

Automated summary

This study comprehensively analyzed cuproptosis in hepatocellular carcinoma (HCC) using various omics approaches. It identified mutation genes and prognostic genes related to cuproptosis, characterized cuproptosis-related hepatocytes and immune patterns, and constructed a prognosis model and CPI index. The clinical relevance of CPI was also analyzed.