Background: Abnormal mucosal inflammation is a critical risk factor for pathogenesis and progression of colorectal cancer (CRC). As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in CRC remains unclear.Methods: A total of 38 pyroptosis-related gene (PRG) expression profiles and clinical information were collected from multiple public datasets. Bioinformatics methods were used to analyze the clinical significance, functional status, immune infiltration, genomic alteration, and drug sensitivity in different subgroups. Whole-genome microarray analysis was performed to analyze the regulation of gut microbiota on the expression of PRGs.Results: Two distinct molecular subtypes were identified and suggested that multilayer PRG alterations were associated with patient clinicopathological features, prognosis, and tumor microenvironment (TME) infiltrating characteristics. Furthermore, we obtained eight PRG signatures by applying differential expression analysis and univariate Cox and Lasso regression analyses. A risk prognosis model was constructed for predicting overall survival (OS) and recurrence-free survival (RFS) based on the PRG signature. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high- and low-risk groups. In addition, the PRG signature was significantly associated with the microsatellite instability (MSI), tumor mutation burden (TMB), cancer stem cell (CSC) index, immunotherapeutic characteristics, and chemotherapeutic drug sensitivity. Moreover, the in vitro experiments had shown that Fusobacterium nucleatum (F.n) could affect the CASP6 expression, which was associated with the chemoresistance to 5-fluorouracil (5-Fu) in CRC.Conclusion: Our findings provided a foundation for future research targeting pyroptosis and a new insight into the prognosis and immune cell infiltration of CRC, and they suggested that F.n might influence CRC progression through pyroptosis.

Objective: Type D personality involves the interaction between negative affectivity with social inhibition and has been associated with an increased risk of coronary artery disease (CAD) progression and coronary plaque vulnerability. However, the underlying mechanisms in the relationship between type D personality and coronary plaque vulnerability remain indeterminate. The present study examined the potential mediating effects of inflammation biomarkers on the association between type D personality and coronary plaque vulnerability in patients with CAD. Methods: A total of 347 patients (mean [standard deviation] age = 56.6 [11.2] years; 29.3% women) with CAD who had culprit coronary plaques were examined for type D personality. The inflammation biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], and tumor necrosis factor α [TNF-α]) were evaluated. Each individual inflammation biomarker was standardized using z scores to calculate inflammation standardized sumscores. Plaque vulnerability of culprit lesions was measured in vivo using optical coherence tomography. Results: The presence of type D personality (38%) was associated with TNF-α, IL-6, and inflammation standardized sumscores (t = 2.74, Cohen d = 0.32, p = .006; t = 4.03, Cohen d = 0.44, p ≤. 001; t = 4.16, Cohen d = 0.11, p = .001, respectively). In addition, the standardized inflammation sumscore was a mediator of the relationship between type D personality and lipid-rich plaques (effect sizes = 0.12, 95% confidence interval = 0.007-0.286, p = .064) and plaque rupture vulnerability (effect sizes = 0.16, 95% confidence interval = 0.043-0.365, p = .024). Analysis of continuous type D scores revealed that TNF-α, IL-6, and inflammation standardized sumscores also mediate the relationship between the primary effect of negative affectivity and plaque vulnerability. Conclusions: Inflammation activation is a potential mediator of the association between type D personality and plaque vulnerability. The negative affectivity component of type D personality might be particularly relevant to the inflammatory aspects of plaque vulnerability.