Identification of Key PANoptosis Regulators in Periodontitis and Chronic Obstructive Pulmonary Disease Using Gene
Suheyla Kaya1, Nail Besli2, Ilhan Onaran3
1Department of Periodontology, Faculty of Dentistry, Istanbul University-Cerrahpaşa, Istanbul 34098, Türkiye.
Background:
Periodontitis (PD) is a chronic inflammatory disease associated with systemic conditions such as chronic obstructive pulmonary disease (COPD). PANoptosis-a form of regulated cell death integrating pyroptosis, apoptosis, and necroptosis-has been implicated in inflammatory diseases, but its role in PD and its overlap with COPD is not well understood.
Methods:
Gene expression datasets for PD and COPD were retrieved from the Gene Expression Omnibus (GEO). Differentially expressed genes were intersected with 78 PANoptosis-related genes. Functional enrichment (GO, KEGG), protein-protein interaction (PPI) network analysis, and machine learning (XGBoost with ROC curves) identified key regulatory genes. Immune infiltration was evaluated, and drug-gene interactions were analyzed using DGIDB.
Results:
Seven PANoptosis-related core genes-ACO1, NLRC4, CASP8, HSPA4, IL1B, MEFV, and CYCS-were identified in both PD and COPD. These genes were enriched in pathways involving inflammasomes, apoptosis, and oxidative stress. Immune analysis showed significant differences in B cells, T cells, dendritic cells, and plasma cells. Potential drug targets, including IL1B and CASP8, were identified.
Conclusions:
This is the first study to link PANoptosis to both PD and COPD. The findings reveal shared molecular mechanisms and suggest PANoptosis-related genes as novel biomarkers and therapeutic targets in chronic inflammatory oral disease.
