A Comprehensive Analysis of the Cuproptosis-Related Gene GCSH in Pan-Cancer with a Focus on Colorectal Cancer

Abstract

Background GCSH, a gene associated with cuproptosis, has been implicated in various cancers, although its role remains incompletely understood. This study aims to conduct a comprehensive analysis of GCSH across multiple cancer types to elucidate its role in tumorigenesis. Methods GCSH expression was analyzed in 33 cancer types using data from TCGA database. Associations with the tumor microenvironment and prognostic value were evaluated. scRNA-seq data from colorectal cancer (CRC) was used to assess GCSH expression in different cell types. Clinical CRC tissues, blood samples, and cell lines were utilized for validation. Functional assays and drug sensitivity tests were performed to further elucidate the role of GCSH. Results GCSH expression varied among different cancers, with notably higher levels in CRC. GCSH demonstrated significant correlations with 22 types of immune cells across the 33 cancers. Generally, GCSH showed a negative correlation with immune scores and immune checkpoint genes. Prognostic analysis revealed that GCSH was associated with outcomes in adrenocortical carcinoma, hepatocellular carcinoma, and stomach adenocarcinoma, although external cohort results did not consistently support these findings. Validation in clinical samples and cell lines confirmed elevated GCSH in CRC. scRNA-seq data indicated higher GCSH expression in both cancerous and immune cells within tumor tissues compared to normal tissues. Functional and pathway analyses in CRC identified key biological roles for GCSH, and a drug sensitivity to GCSH was identified. Conclusions GCSH exerts multifaceted roles in specific cancers and is significantly associated with immune cells and immune checkpoint genes. The study identifies the biological functions of GCSH in CRC and suggests potential drug sensitivities.