Identification of cuproptosis-related subtypes, establishment of a prognostic model and tumor immune landscape in endometrial carcinoma

Cuproptosis, the mechanism of copper-dependent cell death, is distinct from all other known forms of regulated cell death and dependents on mitochondrial respiration. Cuproptosis promises to be a novel treatment, especially for tumors resistant to conventional therapies. We investigated the changes in cuproptosis-related genes (CRGs) in endometrial cancer (EC) cohorts from the merged Gene Expression Omnibus and the Cancer Genome Atlas databases, which could be divided into three distinct CRGclusters. Patients in CRGcluster C would have higher survival probability (P = 0.007), and higher levels of tumor microenvironment (TME) cell infiltration than other CRGclusters. CRG score was calculated via the results of univariate, multivariate cox analysis and least absolute shrinkage and selection operator regression analysis. Patients were divided into two risk subgroups according to the median risk score. Low-risk patients exhibited a more favorable prognosis, higher immunogenicity, and greater immunotherapy efficacy. Besides, CRG scores were strongly correlated to copy number variation, immunophenoscore, tumor mutation load, cancer stem cell index, microsatellite instability, and chemo-sensitivity. The c-index of our model is 0.702, which is higher than other four published model. The results proved that our model can distinguish EC patients with high-risk and low-risk and accurately predict the prognosis of EC patients. It will provide new ideas for clinical prognosis and precise treatments.

Automated summary

Cuproptosis, a mechanism of copper-dependent cell death, has the potential to be a new treatment for tumors resistant to conventional therapies. By analyzing changes in cuproptosis-related genes in endometrial cancer cohorts, three distinct gene clusters were identified, with patients in one cluster having higher survival probability and tumor microenvironment cell infiltration levels. A risk scoring system based on these genes can stratify patients into high-risk and low-risk groups, where low-risk patients have better prognosis and immunotherapy efficacy. Furthermore, the gene scores are correlated with other indicators such as copy number variation and tumor mutation load.