Cuproptosis-Mediated Patterns Characterized by Distinct Tumor Microenvironment and Predicted the Immunotherapy Response for Gastric Cancer

[Image: see text] Cuproptosis is a newly discovered programmed cell death process, and several cuproptosis-related genes have been reported to regulate cancer cell proliferation and progression. The association between cuproptosis and tumor microenvironment in gastric cancer (GC) remains unclear. This study aimed to explore multiomics characteristics of cuproptosis-related genes regulating tumor microenvironment and provide strategies for prognosis and prediction of immunotherapy response in GC patients. We collected 1401 GC patients from the TCGA and 5 GEO data sets and identified three different cuproptosis-mediated patterns, each of which shared a distinct tumor microenvironment and different overall survival. The GC patients with high cuproptosis levels were enriched in CD8+ T cells and had a better prognosis. Whereas, the low cuproptosis level patients were associated with inhibitory immune cell infiltration and had the worst prognosis. In addition, we constructed a 3-gene (AHCYL2, ANKRD6 and FDGFRB) cuproptosis-related prognosis signature (CuPS) via Lasso-Cox and multivariate Cox regression analysis. The GC patients in the low-CuPS subgroup had higher TMB levels, MSI-H fractions, and PD-L1 expression, which suggests a better immunotherapy response. Therefore, the CuPS might have the potential value for predicting prognosis and immunotherapy sensitivity in GC patients.