Cuproptosis-related gene PDHX and heat stress-related HSPD1 as potential key drivers associated with cell stemness, aberrant metabolism and immunosuppression in esophageal carcinoma.

BACKGROUND:Heat stress is fundamental to esophageal carcinoma (ESCA) oncogenesis and progression. Heat stress damages epithelial structure, causing aberrant 'cell death-repair' patterns of esophagus cells and thereby driving tumor occurrence and progression. However, due to the distinctive functions and crosstalk of regulatory cell death (RCD) patterns, the specific cell deaths in ESCA malignancy are still unclear. METHODS:We analyzed the key regulatory cell death genes involved in heat stress and ESCA progression by using The Cancer Genome Atlas-ESCA database. The least absolute shrinkage and selection operator (LASSO) algorithm was used to filter the key genes. The one-class logistic regression (OCLR) and quanTIseq methods were used to evaluate the cell stemness and immune cell infiltration in ESCA samples. Cell counting kit-8 (CCK8) and wound healing assays were performed to assess the proliferation and migration of cells. RESULTS:We found that cuproptosis may be a potential risk factor of heat stress-related ESCA. Two interrelated genes, HSPD1 and PDHX, were associated with heat stress and cuproptosis and played a role in cell survival, proliferation, migration, metabolism and immunosuppression. CONCLUSIONS:We found that cuproptosis promoted ESCA related to heat stress, offering a new therapeutic opportunity to treat this malignant disorder.