Identification of Cuproptosis-Associated Prognostic Gene Expression Signatures from 20 Tumor Types.

Simple Summary: Non-apoptotic modes of cell death have gained increasing attention in the past few years. Cuproptosis is a copper-dependent cell death mechanism that is involved in numerous diseases, including cancer. The relevance of cuproptosis for the survival times of cancer patients is still incompletely understood. We have investigated cuproptosis-related genes based on their mRNA expression and statistical relationship to the survival times of patients by using Kaplan–Meier statistics. Further, we have investigated the possible interactions of the genes with signaling networks. Our study has shown that cuproptosis may play an important role in hepatocellular carcinoma, renal clear cell carcinoma, papillary renal cell carcinoma, and lung adenocarcinoma. We identified gene signatures consisting of nine to twenty-one genes in the above four tumor types, and we have shown that a high mRNA expression of 63/124 cuproptosis-associated genes significantly correlated with shorter survival times of cancer patients. We investigated the mRNA expression of 124 cuproptosis-associated genes in 7489 biopsies from 20 different tumor types of The Cancer Genome Atlas (TCGA). The KM plotter algorithm has been used to calculate Kaplan–Meier statistics and false discovery rate (FDR) corrections. Interaction networks have been generated using Ingenuity Pathway Analysis (IPA). High mRNA expression of 63 out of 124 genes significantly correlated with shorter survival times of cancer patients across all 20 tumor types. IPA analyses revealed that their gene products were interconnected in canonical pathways (e.g., cancer, cell death, cell cycle, cell signaling). Four tumor entities showed a higher accumulation of genes than the other cancer types, i.e., renal clear cell carcinoma (n = 21), renal papillary carcinoma (n = 13), kidney hepatocellular carcinoma (n = 13), and lung adenocarcinoma (n = 9). These gene clusters may serve as prognostic signatures for patient survival. These signatures were also of prognostic value for tumors with high mutational rates and neoantigen loads. Cuproptosis is of prognostic significance for the survival of cancer patients. The identification of specific gene signatures deserves further exploration for their clinical utility in routine diagnostics. [ABSTRACT FROM AUTHOR]