Characterization of PANoptosis patterns predicts survival and immunotherapy response in gastric cancer

Accumulating evidence suggests that pyroptosis, apoptosis and necroptosis are deeply involved in cancer immunity. However, the role of PANoptosis in gastric cancer (GC) remains unexplored. In this study, we identified three distinct PANoptosis patterns in 1316 patients with GC, each PANoptosis pattern has its own molecular, clinical and immunological features. A scoring system named PANscore was constructed to quantify the PANoptosis patterns of the individual patients with GC. The low PANscore group had a higher response rate to immunotherapy and had a better prognosis. The predictive ability of the PANscore for prognosis and immunotherapy response was validated in multiple independent cohorts. Pan-cancer analyses showed that high PANscore was significantly associated with low expression of immune checkpoints, high expression of TGF-β, dense infiltration of cancer-associated fibroblasts and macrophage M2. In conclusion, characterization of PANoptosis patterns provides a roadmap for patient stratification, not only in GC but also across pan-cancer.