Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma

Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and is characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remain elusive. Here, we systematically assessed the transcriptional and genetic alterations of CRGs in ESCA. We identified a CRGs signature for ESCA patients. A 6-CRGs signature was constructed by the 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 a high CRGs score was significantly correlated with worse 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 increased sensitivity to PI3K-AKT pathway inhibitors. In addition, patients with high CRGs tend to hold more mutation load and abnormal APOBEC mutation. Notably, a higher CRGs score was anomalously associated with more immune infiltration, which could explain its malignancy by increased PD-L1 stability and a higher proportion of bystander T cells. In conclusion, our report revealed the significance of cuproptosis in ESCA and may have therapeutic potential in activating the bystander T cells.

Automated summary

This study systematically assessed the transcriptional and genetic alterations of cuproptosis-related genes (CRGs) in esophageal carcinoma (ESCA). A CRGs signature was identified and found to significantly stratify ESCA patients' survival. Higher CRGs scores were associated with worse overall survival, higher pathology grades, aberrant cell adhesion, and increased sensitivity to PI3K-AKT pathway inhibitors. Additionally, high CRGs were correlated with increased mutation load and abnormal APOBEC mutation. Interestingly, higher CRGs scores were anomalously associated with more immune infiltration, possibly explaining its malignancy through increased PD-L1 stability and a higher proportion of bystander T cells.