Pyroptosis may play a crucial role in modifications of the immune microenvironment in periodontitis

Published studies proved that both pyroptosis and periodontitis owned a substantial relationship with immunity, and recent research revealed a solid correlation between periodontitis and pyroptosis. While abundant findings have confirmed pyroptosis has a strong impact on the tumor microenvironment, the function of pyroptosis in influencing the periodontitis immune microenvironment remains poorly understood. Thus, we aimed to identify pyroptosis-related genes whose expression signature can well discriminate periodontitis from healthy controls and to comprehend the role of pyroptosis in the periodontitis immune microenvironment.

The periodontitis-related datasets were acquired from the Gene Expression Omnibus (GEO) database. A series of bioinformatics analyses were conducted to investigate the underlying mechanism of pyroptosis in the periodontitis immune microenvironment. Infiltrating immunocytes, immunological reaction gene sets, and the human leukocyte antigen (HLA) gene were all investigated as potential linkages between periodontitis immune microenvironment and pyroptosis.

Twenty-one pyroptosis-related genes were dysregulated. A four-mRNA combined classification model was constructed, and the receiver operating characteristic (ROC) curve analysis demonstrated its prominent classification capabilities. Subsequently, the mRNA levels of the four hub markers (CYCS, CASP3, NOD2, CHMP4B) were validated by quantitative real-time PCR (qRT-PCR). The correlation coefficients between each hub gene and immune characteristics were calculated, and CASP3 exhibited the most significant correlations with the immune characteristics. Furthermore, distinct pyroptosis-related expression patterns were revealed, along with immunological features of each pattern. Afterward, we discovered 1868 pyroptosis phenotype-related genes, 134 of which were related to immunity. According to the functional enrichment analysis, these 134 genes were closely related to cytokine signaling in immune system, and defense response. Finally, a co-expression network was constructed via the 1868 gene expression profiles.

Four hub mRNAs (CYCS, CASP3, NOD2, and CHMP4B) formed a classification model and concomitant results revealed the crucial role of pyroptosis in the periodontitis immune microenvironment, providing fresh insights into the etiopathogenesis of periodontitis and potential immunotherapy.