Cuproptosis-related classification and personalized treatment in lower-grade gliomas to prompt precise oncology

BackgroundCuproptosis is implicated in regulating tricarboxylic acid cycle and associated with tumor therapeutic sensitivity, patient outcomes and tumorigenesis. However, the classification and prognostic effect of cuproptosis-associated genes (CAGs), the relationship between cuproptosis and tumor microenvironment (TME) and the treatment of lower-grade glioma (LrGG) remain enigmatic. MethodsThe genetic and transcriptional alterations, prognostic value and classification related to cuproptosis were systematically analyzed. Subtypes of cuproptosis and cuproptosis score (Cuscore) were constructed and further confirmed by two external cohorts. The relationships between cuproptosis and TME, prognosis, and treatment response were also evaluated. ResultsFour clusters were identified based on cuproptosis-associated genes. The associations between cuproptosis-associated clusters and clinical features, prognosis, immune cell infiltration, and chemotherapy sensitivity were observed. The Cuscore is an independent prognostic indicator in LrGG patients. The nomogram is constructed according to Cuscore and clinical characteristics, and has good predictive ability and calibration. Patients with high Cuscore had a worse prognosis and advanced performance. A higher Cuscore also indicated a higher stromal score, abundant immune infiltration, and increased tumor mutation burden. A high Cuscore was remarkably related to immune checkpoint inhibitors, immunotherapy response and immune phenotype. ConclusionsThis study demonstrates the clinical effect of CAGs, and suggests that cuproptosis could be a potential therapeutic target in LrGG.

Automated summary

This study systematically analyzed the classification, prognostic value, and relationship with tumor microenvironment (TME) of cuproptosis-associated genes (CAGs). Four clusters of CAGs were identified, and their associations with clinical features, prognosis, immune cell infiltration, and chemotherapy sensitivity were observed. The cuproptosis score (Cuscore) was found to be an independent prognostic indicator in lower-grade glioma (LrGG) patients. A high Cuscore was associated with worse prognosis, immune infiltration, and increased tumor mutation burden, as well as with immune checkpoint inhibitors, immunotherapy response, and immune phenotype.