Prognostic signature of esophageal adenocarcinoma based on pyroptosis-related genes.

Background: The role of pyroptosis-related genes (PRGs) in esophageal adenocarcinoma (EAC) remains unknown.

Methods: In this study, the first PRGs prognostic signature (PPS) of EAC was constructed based on the results of multivariate stepwise Cox regression analysis. Based on 1,047 samples of EAC and normal esophagus (NE), differentially expressed PRGs were selected for the establishment of the PPS. The discrimination effect of this PPS was detected by receiver operating characteristic curves, and the prognosis value of this PPS was determined through Cox regression analysis and Kaplan-Meier curves. Net benefits of the EAC patients from the nomogram (constructed based on the PPS and some clinical parameters) were assessed via decision curve analysis. The potential molecular mechanism of the PPS in EAC was explored via gene set enrichment analysis. The ability of PPS to distinguish EAC and NE was evaluated based on the results of summary receiver operating characteristic curves.

Results: The significant prognostic value of PPS can be observed at all of the training cohort, test cohort, and validation cohort, such as its independent risk role in the prognosis of the EAC patients (hazard ratio > 0; 95% CI not including 0). The positive net benefits of the nomogram for the EAC patients can be detected via decision curve analysis, and the potential molecular mechanism of the PPS in EAC is likely related to cell pyroptosis. Last, some of the PRGs (particularly CASP5) included in this PPS specifically support its feasibility for identifying EAC (area under the curves > 0.7).

Conclusions: The construction of this PPS in EAC enhances the present understanding of the relationship between PRGs and EAC, thus representing a novel approach to the clinical identification and management of EAC based on PRGs.