Comprehensive Analysis of Pyroptosis-related Genes for the Prognosis of Esophageal Cancer

Abstract Background Esophageal cancer (EC), known for its high malignancy and difficulty in treatment, has seen a significant increase in incidence in recent years. Studies on prognosis of EC are extremely urgent to provide personalized medicine which will benefit more patients individually. Pyroptosis, an inflammatory form of programmed cell death triggered by caspase-1/4/5/11 which is activated by some inflammasomes has been connected to cancer in recent studies. However, the association between pyroptosis-related genes and esophageal cancer has not been elucidated, and their vital role in the development and prognosis of esophageal cancer needs further research. Methods We obtained 290 samples from both TCGA and GEO database,including 11 normal people and 279 EC patients. Then we screened pyroptosis-related regulators that were differentially expressed in normal esophageal and cancer tissues. We next exerted univariate Cox regression analysis and LASSO analysis to further choose key genes.Validation of these genes’ expression in cells was also conducted in vitro. Using these genes and other clinical features, we next constructed a risk model and a nomogram for predicting the prognosis of EC patients. Functions of pyroptosis-related genes and their relevance to clinical characteristics were discussed through two clustering analyses, Finally, we constructed a pyroptosis score system to predict the prognosis of EC. Results We finally screened 32 differentially expressed genes between normal and tumor tissues.And 8 key genes were identified after univariate Cox regression and LASSO analysis. Then the risk model and nomogram built based on them both showed strong predictive power according to our survival curves and ROC curves.Our subsequent invitro validation on key genes above also appeared high agreement with the regression analysis result. Finally, we calculated the pyroptosis score and it showed strong relationship with clinical features. Conclusion Pyroptosis-related genes are intimately related with EC and can be used to predict the prognosis of EC, which may also provide novel therapeutic schedule for EC patients.