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

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 pyroptosisrelated
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 pyroptosisrelated
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 pyroptosisrelated
mechanisms.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87572
Date23 October 2023
CreatorsNing, Wanchen, Acharya, Aneesha, Li, Simin, Schmalz, Gerhard, Huang, Shaohong
PublisherFrontiers Media S.A.
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation862049, 10.3389/fimmu.2022.862049

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