A novel and robust pyroptosis-related prognostic signature predicts prognosis and response to immunotherapy in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal tumor, has a poor prognosis and high mortality rate. Pyroptosis could regulate tumor cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in ESCC remains unclear. This study selected 33 PRGs, and finally identified 29 PRGs that were differentially expressed between ESCC and normal esophageal tissues. The genetic mutation variation landscape of PRG in ESCC was also summarised. Based on consensus clustering for the 33 PRGs, all ESCC patients could be divided into two subtypes. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in cytokine production, interleukin-1 production, and the NOD-like receptor signalling pathway. We created a prognostic PRG signature based on least absolute shrinkage and selection operator regression and Cox regression analysis with good survival prediction ability in both GEO and TCGA cohorts. Combined with the clinical characteristics, signature-based risk score was found to be an independent factor for predicting the OS of ESCC patients. A nomogram with enhanced precision for forecasting ESCC was established based on various independent prognostic elements. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumor mutation burden, microsatellite instability, immune checkpoint, and drug sensitivity. Finally, we validated the expression of four PRGs in ESCC cell lines and tissues samples. In conclusion, the PRGs exerted significant effects on tumor immunity and prognosis of ESCC.