Exploration of cross-talk and pyroptosis-related gene signatures and molecular mechanisms between periodontitis and diabetes mellitus via peripheral blood mononuclear cell microarray data analysis

Hang Chen; Limin Peng; Zhenxiang Wang; Yujuan He; Song Tang; Xiaonan Zhang

doi:10.1016/j.cyto.2022.156014

Exploration of cross-talk and pyroptosis-related gene signatures and molecular mechanisms between periodontitis and diabetes mellitus via peripheral blood mononuclear cell microarray data analysis

Cytokine. 2022 Nov:159:156014. doi: 10.1016/j.cyto.2022.156014. Epub 2022 Sep 7.

Authors

Hang Chen¹, Limin Peng¹, Zhenxiang Wang¹, Yujuan He², Song Tang¹, Xiaonan Zhang³

Affiliations

¹ College of Stomatology, Chongqing Medical University, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, China.
² Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, China.
³ College of Stomatology, Chongqing Medical University, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, China. Electronic address: 500133@hospital.cqmu.edu.cn.

PMID: 36084605
DOI: 10.1016/j.cyto.2022.156014

Abstract

Objectives: This bioinformatics study is aimed at identifying cross-talk genes, pyroptosis-related genes, and related pathways between periodontitis (PD) and diabetes mellitus (DM), which includes type 1 diabetes (T1DM) and type 2 diabetes (T2DM).

Methods: GEO datasets containing peripheral blood mononuclear cell (PBMC) data of PD and DM were acquired. After batch correction and normalization, differential expression analysis was performed to identify the differentially expressed genes (DEGs). And cross-talk genes in the PD-T1DM pair and the PD-T2DM pair were identified by overlapping DEGs with the same trend in each pair. The weighted gene coexpression network analysis (WGCNA) algorithm helped locate the pyroptosis-related genes that are related to cross-talk genes. Receiver-operating characteristic (ROC) curve analysis confirmed the predictive accuracy of these hub genes in diagnosing PD and DM. The correlation between hub genes and the immune microenvironment of PBMC in these diseases was investigated by Spearman correlation analysis. The experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. Subnetwork analysis helped identify the key pathway connecting DM and PD.

Results: Hub genes in the PD-T1DM pair (HBD, NLRC4, AIM2, NLRP2) and in the PD-T2DM pair (HBD, IL-1Β, AIM2, NLRP2) were identified. The similarity and difference in the immunocytes infiltration levels and immune pathway scores of PD and DM were observed. ROC analysis showed that AIM2 and HBD exhibited pleasant discrimination ability in all diseases, and the subnetwork of these genes indicated that the NOD-like receptor signaling pathway is the most potentially relevant pathway linking PD and DM.

Conclusion: HBD and AIM2 could be the most relevant potential cross-talk and pyroptosis-related genes, and the NOD-like receptor signaling pathway could be the top candidate molecular mechanism linking PD and DM, supporting a potential pathophysiological relationship between PD and DM.

Keywords: Bioinformatics; Cross-talk; Diabetes mellitus; Periodontitis; Pyroptosis.

Publication types

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

MeSH terms

Computational Biology
Data Analysis
Diabetes Mellitus, Type 1*
Diabetes Mellitus, Type 2* / genetics
Gene Expression Profiling
Humans
Leukocytes, Mononuclear
NLR Proteins / genetics
Periodontitis*
Pyroptosis / genetics

Substances

NLR Proteins