Stomatological Hospital, Southern Medical University, Guangzhou, China.
Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pune, India.
Front Immunol. 2022 Jun 29;13:862049. doi: 10.3389/fimmu.2022.862049. eCollection 2022.
This study aims to identify pyroptosis-related genes (PRGs), their functional immune characteristics, and distinct pyroptosis-related clusters in periodontitis.
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).
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.
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.
本研究旨在鉴定牙周炎中与细胞焦亡相关的基因（PRGs）、它们的功能免疫特征以及不同的细胞焦亡相关聚类。
通过合并 GSE10334、GSE16134 的表达谱和之前文献中获得的 PRGs 以及分子特征数据库（MSigDB），确定差异表达（DE）-PRGs。应用最小绝对收缩和选择算子（LASSO）回归筛选预后 PRGs 并构建预后模型。应用共识聚类确定与细胞焦亡相关的聚类。进行功能分析和单样本基因集富集分析（ssGSEA）以探索聚类的生物学特征和免疫活性。使用加权相关网络分析（WGCNA）定义与细胞焦亡相关的枢纽模块。
在 26 个与牙周炎相关的 DE-PRGs 中，与高迁移率族蛋白 B1（HMGB1）和 SR 相关 CTD 相关因子 11（SCAF11）的正相关性最高。通过 LASSO 模型建立了一个基于 14 个 PRGs 的特征。此外，基于 14 个预后 PRGs 获得了三个与细胞焦亡相关的聚类。Caspase 3（CASP3）、Granzyme B（GZMB）、白细胞介素 1 阿尔法（IL1A）、白细胞介素 1 贝塔（B）、白细胞介素 6（IL6）、磷酯酶 C 伽马 1（PLCG1）和 PYD 和 CARD 结构域包含（PYCARD）在三个聚类中失调。在牙周炎的三个与细胞焦亡相关的聚类中鉴定了不同的生物学功能和免疫活性，包括人类白细胞抗原（HLA）基因表达、免疫细胞浸润和免疫途径活性。此外，与内质网应激相关功能相关的粉色模块与聚类 2 相关，被认为是与细胞焦亡相关的枢纽模块。
本研究确定了 14 个关键的与细胞焦亡相关的基因、三个不同的与细胞焦亡相关的聚类和一个描述牙周炎发病机制和免疫微环境调节中细胞焦亡的几个分子方面的与细胞焦亡相关的基因模块，并强调了与细胞焦亡相关机制的功能异质性。
