Abstract
Despite mounting evidence linking pyroptotic cell death to tumor growth, the clinical significance and disease mechanism of pyroptosis in cancer remain uncertain. In this study, we established a unique gene signature (π signature) that can be used as a predictive and prognostic tool in pyroptosis-related cancer subtypes. We found that the 13 core pyroptosis genes exerted opposite prognostic effects in different cancer types, which were subgrouped as pyroptosis positively related cancer and pyroptosis negatively related cancer. Subsequently, π signature was identified separately from the hub genes in pyroptosis positively related cancer and pyroptosis negatively related cancer subtypes. It was shown that π signature was well correlated with patient survival, pathological stages, tumor lymphocyte infiltration, and immunotherapy response. π signature was also applied as a predictive tool for chemotherapy drug responses and used as an independent factor for patient overall survival prediction. In short, this elaborated genetic signature could help us understand the oncogenic mechanism and pave the way for further therapeutic strategies based on pyroptosis.