Construction of PANoptosis signature: Novel target discovery for prostate cancer immunotherapy

PANoptosis pathway gene sets encompassing pyroptosis, apoptosis, and necroptosis were identified from the MSigDB database. We analyzed the perturbations and crosstalk in the PANoptosis pathway in prostate adenocarcinoma (PRAD), including gene mutation, transcription, methylation, and clin-ical features. By constructing a PANoptosis signature, we accurately predicted the prognosis and immunotherapeutic response of PRAD patients. We further explored the molecular features and immunological roles of the signature, dividing pa-tients into high-and low-score groups. Notably, the high-score group correlated with better survival outcomes and immuno-therapeutic responses, as well as a higher mutation frequency and enrichment score in the PANoptosis and HALLMARK pathways. The PANoptosis signature also enhanced overall antitumor immunity, promoted immune cell infiltration, upre-gulated immune checkpoint regulators, and revealed the cold tumor characteristics of PRAD. We also identified potential drug targets based on the PANoptosis signature. These findings lead the way in identifying novel prognostic markers and ther-apeutic targets for patients with PRAD.

Automated summary

We identified PANoptosis pathway gene sets and analyzed their perturbations and crosstalk in prostate adenocarcinoma. By constructing a PANoptosis signature, we accurately predicted prognosis and immunotherapeutic response. The signature enhanced overall antitumor immunity, immune cell infiltration, and revealed the cold tumor characteristics of PRAD.