Molecular subtypes of cuproptosis regulators and their correlation with clinical prognosis and immune response in glioma.

Cuproptosis is a newly described form of cell death. However, nothing is known about the roles of cuproptosis regulators in glioma. First, we explored the characteristics of cuproptosis molecular subtypes and relevant tumor microenvironment (TME) immune cell infiltration patterns in glioma. Using unsupervised clustering analysis, we identified two cuproptosis subtypes and three gene clusters that exhibited different clinical characteristics and TME cell infiltration patterns. Then, we developed and validated a cuproptosis-related prognostic model for predicting the overall survival of glioma patients. We established a risk score tool based on a nomogram to assess the clinical applicability of the cuproptosis model. A high cuproptosis risk score with high immune cell infiltration level, tumor mutation burden, gene alterations, and immunity activation had an unfavorable overall survival. Next, we identified possible competing endogenous ribonucleic acid regulatory networks based on significantly differentially expressed genes between high-risk and low-risk groups and screened several candidate small molecular compounds that may improve chemotherapy. Data from IMvigor and GSE78200 showed that the cuproptosis score affected the prognosis of patients who received immunotherapy. Our study indicated that cuproptosis regulators are involved in TME immune infiltration and impact the clinical prognosis in glioma. It is necessary for clinical practice to develop different therapeutic strategies according to the different phenotypes associated with immune response. The present findings provide new insight for improving immunotherapy strategies and individualized treatment in glioma.