Roles of Pyroptosis-Related Genes in the Diagnosis and Subtype Classification of Periodontitis

Pyroptosis is widely involved in many diseases, including periodontitis. Nonetheless, the functions of pyroptosis-related genes (PRGs) in periodontitis are still not fully elucidated. Therefore, we aimed to investigate the role of PRGs in periodontitis. Three datasets (GSE10334, GSE16134, and GSE173078) from the Gene Expression Omnibus (GEO) were selected to analyze the differences in expression values of the PRGs between nonperiodontitis and periodontitis tissue samples using difference analysis. Following this, five hub PRGs (charged multivesicular body protein 2B, granzyme B, Z-DNA-binding protein 1, interleukin-1β, and interferon regulatory factor 1) predicting periodontitis susceptibility were screened by establishing a random forest model, and a predictive nomogram model was constructed on the basis of these genes. Decision curve analysis suggested that the PRG-based predictive nomogram model could provide clinical benefits to patients. Three distinct PRG patterns (cluster A, cluster B, and cluster C) in the periodontitis samples were revealed according to the 48 significant PRGs, and the difference in the immune cell infiltration among the three patterns was explored. We observed that all infiltrating immune cells, except type 2 T helper cells, differ significantly among the three patterns. To quantify the PRG patterns, the PRG score was calculated by principal component analysis. According to the results, cluster B had the highest PRG score, followed by cluster A and cluster C. In conclusion, PRGs significantly contribute to the development of periodontitis. Our study of PRG patterns might open up a new avenue to guide individualized treatment plans for patients with periodontitis.

[1]  Yujuan He,et al.  Pyroptosis may play a crucial role in modifications of the immune microenvironment in periodontitis. , 2022, Journal of periodontal research.

[2]  Lichun Lu,et al.  Machine Learning-Based Integration Develops a Pyroptosis-Related lncRNA Model to Enhance the Predicted Value of Low-Grade Glioma Patients , 2022, Journal of oncology.

[3]  Ni Zeng,et al.  Identification of the Shared Gene Signatures and Biological Mechanism in Type 2 Diabetes and Pancreatic Cancer , 2022, Frontiers in Endocrinology.

[4]  Yanshan Fang,et al.  CHMP2B regulates TDP-43 phosphorylation and cytotoxicity independent of autophagy via CK1 , 2021, The Journal of cell biology.

[5]  G. Neale,et al.  ADAR1 restricts ZBP1-mediated immune response and PANoptosis to promote tumorigenesis. , 2021, Cell reports.

[6]  Hao Li,et al.  Integrated Analysis of Weighted Gene Coexpression Network Analysis Identifying Six Genes as Novel Biomarkers for Alzheimer's Disease , 2021, Oxidative medicine and cellular longevity.

[7]  P. Papapanou,et al.  Differential DNA methylation and mRNA transcription in gingival tissues in periodontal health and disease. , 2021, Journal of clinical periodontology.

[8]  Jingjing Cai,et al.  Caspase-11-Gasdermin D-Mediated Pyroptosis Is Involved in the Pathogenesis of Atherosclerosis , 2021, Frontiers in Pharmacology.

[9]  W. Ding,et al.  IRF1 regulates the progression of colorectal cancer via interferon-induced proteins , 2021, International journal of molecular medicine.

[10]  H. Qi,et al.  A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer , 2021, Cell Death Discovery.

[11]  Han Xiao,et al.  Glycogen synthase kinase-3β (GSK-3β) deficiency inactivates the NLRP3 inflammasome-mediated cell pyroptosis in LPS-treated periodontal ligament cells (PDLCs) , 2021, In Vitro Cellular & Developmental Biology - Animal.

[12]  D. Zou,et al.  Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis , 2021, Frontiers in Cell and Developmental Biology.

[13]  T. Kanneganti,et al.  NLRP3 inflammasome in cancer and metabolic diseases , 2021, Nature Immunology.

[14]  Y. Shang,et al.  Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database , 2021, Frontiers in Genetics.

[15]  M. Shin,et al.  Association of GZMB polymorphisms and susceptibility to non-segmental vitiligo in a Korean population , 2021, Scientific reports.

[16]  I. Lamster,et al.  Current concepts in the management of periodontitis. , 2020, International dental journal.

[17]  T. Kanneganti,et al.  The regulation of the ZBP1‐NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis) , 2020, Immunological reviews.

[18]  B. Zhang,et al.  m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer , 2020, Molecular Cancer.

[19]  M. Shao,et al.  Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review , 2020, International Journal of Oral Science.

[20]  Feng Chen,et al.  Development and validation of an immune gene-set based Prognostic signature in ovarian cancer , 2018, EBioMedicine.

[21]  D. Granville,et al.  Granzyme B in skin inflammation and disease. , 2017, Matrix biology : journal of the International Society for Matrix Biology.

[22]  W. Liu,et al.  NLRP6 Induces Pyroptosis by Activation of Caspase-1 in Gingival Fibroblasts , 2018, Journal of dental research.

[23]  S. Ji,et al.  Caspase-4 activation by a bacterial surface protein is mediated by cathepsin G in human gingival fibroblasts , 2017, Cell Death and Differentiation.

[24]  J. Slots.  Periodontitis: facts, fallacies and the future. , 2017, Periodontology 2000.

[25]  M. Huber,et al.  Reciprocal regulation of the Il9 locus by counteracting activities of transcription factors IRF1 and IRF4 , 2017, Nature Communications.

[26]  Si Ming Man,et al.  Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases , 2017, Immunological reviews.

[27]  E. Dueber,et al.  Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions. , 2017, Trends in immunology.

[28]  S. Yao,et al.  NLRP3 Inflammasome in Neurological Diseases, from Functions to Therapies , 2017, Front. Cell. Neurosci..

[29]  Tao Huang,et al.  Analysis of cancer-related lncRNAs using gene ontology and KEGG pathways , 2017, Artif. Intell. Medicine.

[30]  J. Lieberman,et al.  Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores , 2016, Nature.

[31]  T. Kurita-Ochiai,et al.  Regulation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated periodontal disease , 2016, Inflammation Research.

[32]  I. Chapple,et al.  Molecular aspects of the pathogenesis of periodontitis. , 2015, Periodontology 2000.

[33]  G. Hajishengallis,et al.  Periodontitis: from microbial immune subversion to systemic inflammation , 2014, Nature Reviews Immunology.

[34]  U. Rao,et al.  Immunohistochemical Analysis of Expressions of RB1, CDK4, HSP90, cPLA2G4A, and CHMP2B Is Helpful in Distinction between Myxofibrosarcoma and Myxoid Liposarcoma , 2014, International journal of surgical pathology.

[35]  P. Pavlidis,et al.  Gingival Tissue Transcriptomes Identify Distinct Periodontitis Phenotypes , 2014, Journal of dental research.

[36]  A. Kantarcı,et al.  Inflammatory and immune pathways in the pathogenesis of periodontal disease. , 2014, Periodontology 2000.

[37]  C. Garlanda,et al.  The interleukin-1 family: back to the future. , 2013, Immunity.

[38]  Matthew D. Wilkerson,et al.  ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking , 2010, Bioinform..

[39]  Paul Pavlidis,et al.  Transcriptomes in Healthy and Diseased Gingival Tissues , 2008 .

[40]  T. Taniguchi,et al.  Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53. , 1999, Genes & development.