Background: The potential role of pyroptosis in tumor microenvironment (TME) reprogramming and immunotherapy has received increasing attention. As most studies have concentrated on a single TME cell type or a single pyroptosis regulator (PR), the overall TME cell-infiltrating characteristics mediated by the integrated roles of multiple PRs have not been comprehensively recognized. Methods: This study curated 33 PRs and conducted consensus clustering to identify distinct pyroptosis patterns in gastric cancer (GC) patients. A single-sample gene set enrichment analysis algorithm was used to quantify the infiltration density of TME immune cells and the enrichment scores of well-defined biological signatures. The pyroptosis patterns of individuals were quantified using a principal component analysis algorithm called the pyroptosis score (PS). Results: Three distinct pyroptosis patterns with significant survival differences were identified from 1422 GC samples; these patterns were closely associated with three TME cell-infiltrating landscapes—namely, the immune-inflamed, immune-excluded, and immune-desert phenotypes. The PS model generated on the basis of the pyroptosis pattern-related signature genes could accurately predict the TME status, existing molecular subtypes, genetic variation, therapeutic response, and clinical outcome; among which, a relatively high PS was highly consistent with immune activation, molecular subtypes with survival advantages, high tumor mutation burden, high microsatellite instability, and other favorable characteristics. In particular, from the Cancer Genome Atlas database, the PS model exhibited significant prognostic relevance in a pan-cancer analysis, and patients with a relatively high PS exhibited durable therapeutic advantages and better prognostic benefits in anti-PD1/L1 therapy. Conclusions: This study demonstrates that pyroptosis is prominently correlated with TME diversity and complexity, and quantification of the pyroptosis patterns of individuals will enhance our cognition of TME infiltration landscapes and help in formulating more effective immunotherapeutic strategies.

Background: This prospective study aimed to explore the correlation between circulating mitochondrial DNA (mtDNA), intestinal barrier function impairment, and postoperative SIRS in patients undergoing gastrointestinal surgery. Methods: Patients were recruited into this study after signing an informed consent form. Circulating mitochondrial DNA and serum DAO concentrations were measured preoperatively and on day 1 and day 7 postoperatively. Postoperative vitals, routine tests, and biochemical indicators were recorded in detail. Results: Forty patients undergoing gastrointestinal surgery were recruited for and completed this study. Patients were divided into non-fever, fever, and SIRS groups according to their postoperative temperature and other corresponding indexes. The mtDNA was expressed as the number of PCR cycles using three specific sequences. Circulating mtDNA tended to increase in patients after gastrointestinal surgery, but the difference was not significant. Nevertheless, mtDNA in the SIRS group was significantly higher than in patients in the fever and non-fever groups (p < 0.05). Serum DAO showed a trend of increase on the first day after surgery compared with that before surgery, but the difference was not significant (p > 0.05). However, patients in the SIRS group showed a significant increase (p < 0.05) compared with the others. Both circulating mtDNA and DAO showed a downward trend on the seventh day after surgery. Conclusions: Circulating mtDNA presented a trend of increase after gastrointestinal surgery, and the degree of the increased fold was related to the extent of the inflammation response. In general, the intestinal barrier damage indicator DAO was the same as mtDNA and tended to increase after gastrointestinal surgery and then gradually decrease, which may play a synergistic role in inducing postoperative fever and SIRS.