Cuproptosis-related genes signature is associated with tumor progression, PD-L1 stability and bystander T cells in esophageal carcinoma

Abstract

Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remains elusive. Here, we systematically assessed the transcriptional and genetic alterations of cuproptosis-related genes (CRGs) in ESCA. We identified a cuproptosis-related genes (CRGs) signature for ESCA patients. A 6-CRGs signature was constructed by Least absolute shrinkage and selection operator (LASSO) regression analysis along with the univariate cox regression analysis and differential genes analysis. The CRGs score could significantly stratify ESCA patients’ survival and high CRGs score was significantly correlated with bad overall survival. Moreover, higher CRGs score indicated higher pathology grades and aberrant cell adhesion, possibly via the PI3K-AKT pathway, which could also underly their more sensitivity to PI3K-AKT pathway inhibitors as well. In addition, patients with high CRGs were tend to hold more mutation loading and abnormal APOBEC mutation. Notably, higher CRGs score was anomalously associated with more immune infiltration, while could explain its malignancy by more PD-L1 stability and more proportion of bystander T cells. In conclusion, our report revealed the significance of cuproptosis in ESCA and held a potential therapeutic promise of activating the bystander T cells.