Identification of Key Pyroptosis-Related Genes and Distinct Pyroptosis-Related Clusters in Periodontitis

Wanchen Ning; Aneesha Acharya; Simin Li; Gerhard Schmalz; Shaohong Huang

doi:10.3389/fimmu.2022.862049

Identification of Key Pyroptosis-Related Genes and Distinct Pyroptosis-Related Clusters in Periodontitis

Front Immunol. 2022 Jun 29:13:862049. doi: 10.3389/fimmu.2022.862049. eCollection 2022.

Authors

Wanchen Ning¹, Aneesha Acharya², Simin Li¹, Gerhard Schmalz³, Shaohong Huang¹

Affiliations

¹ Stomatological Hospital, Southern Medical University, Guangzhou, China.
² Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pune, India.
³ Department of Cariology, Endodontology and Periodontology, University Leipzig, Leipzig, Germany.

Abstract

Aim: This study aims to identify pyroptosis-related genes (PRGs), their functional immune characteristics, and distinct pyroptosis-related clusters in periodontitis.

Methods: Differentially expressed (DE)-PRGs were determined by merging the expression profiles of GSE10334, GSE16134, and PRGs obtained from previous literatures and Molecular Signatures Database (MSigDB). Least absolute shrinkage and selection operator (LASSO) regression was applied to screen the prognostic PRGs and develop a prognostic model. Consensus clustering was applied to determine the pyroptosis-related clusters. Functional analysis and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the biological characteristics and immune activities of the clusters. The hub pyroptosis-related modules were defined using weighted correlation network analysis (WGCNA).

Results: Of the 26 periodontitis-related DE-PRGs, the highest positive relevance was for High-Mobility Group Box 1 (HMGB1) and SR-Related CTD Associated Factor 11 (SCAF11). A 14-PRG-based signature was developed through the LASSO model. In addition, three pyroptosis-related clusters were obtained based on the 14 prognostic PRGs. Caspase 3 (CASP3), Granzyme B (GZMB), Interleukin 1 Alpha (IL1A), IL1Beta (B), IL6, Phospholipase C Gamma 1 (PLCG1) and PYD And CARD Domain Containing (PYCARD) were dysregulated in the three clusters. Distinct biological functions and immune activities, including human leukocyte antigen (HLA) gene expression, immune cell infiltration, and immune pathway activities, were identified in the three pyroptosis-related clusters of periodontitis. Furthermore, the pink module associated with endoplasmic stress-related functions was found to be correlated with cluster 2 and was suggested as the hub pyroptosis-related module.

Conclusion: The study identified 14 key pyroptosis-related genes, three distinct pyroptosis-related clusters, and one pyroptosis-related gene module describing several molecular aspects of pyroptosis in the pathogenesis and immune micro-environment regulation of periodontitis and also highlighted functional heterogeneity in pyroptosis-related mechanisms.

Keywords: immune microenvironment; inflammasome; periodontitis; prognostic; pyroptosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Regulatory Networks
Humans
Periodontitis* / genetics
Prognosis
Pyroptosis* / genetics