Pyroptosis patterns of colon cancer could aid to estimate prognosis, microenvironment and immunotherapy: evidence from multi-omics analysis

Pyroptosis plays a critical role in the occurrence and development of colon cancer (CC). However, the specific mechanisms of pyroptosis patterns on immune regulation and tumor microenvironment (TME) formation in CC remain unclear. Based on 30 pyroptosis-related genes (PRGs), we evaluated the pyroptosis patterns of 1689 CC samples from the Cancer Genome Atlas and the Gene Expression Omnibus databases. The signatures of pyroptosis patterns and PRGs were identified in CC. In addition to systematically associating these patterns with TME cell infiltration characteristics, we constructed a pyroptosis signature score (PPSscore) to quantify pyroptosis patterns in individual tumor patients with immune responses. We discovered three distinct pyroptosis patterns, each with a different survival probability and being biologically relevant. TME infiltrating characteristics of revealed these patterns, consistent with immune-inflamed, immune-desert and immune-excluded phenotypes. Furthermore, a low PPSscore was associated with better clinical benefits. A high PPSscore was associated with a lower chance of survival due to its association with stromal activation. Additionally, two immunotherapy cohorts revealed that patients with lower PPSscore had better immune responses and durable clinical benefits. Our findings indicate that pyroptosis patterns play a vital role in immunoregulation and the formation of TME in CC.