Abstract
OBJECTIVE: The objective of this study is to investigate the role of cuproptosis-related genes (CRGs) in periodontitis using an integrative approach that combines single-cell RNA sequencing (scRNA-seq) and bioinformatic analyses. The study aims to elucidate the connection between copper-induced cell death (cuproptosis) and periodontitis, a prevalent chronic inflammatory oral disease that leads to tooth-supporting tissue damage and eventual tooth loss. METHODS: Differentially expressed genes (DEGs) were identified from the GSE10334 dataset, leading to the discovery of 14 differentially expressed CRGs associated with periodontitis. Subsequent application of least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis pinpointed three key CRGs: MTF1, GLS, and DLST. Single-cell sequencing data analysis was further conducted to explore the expression patterns of these genes, particularly GLS, within immune cells and their association with the immune cell network in periodontal tissues. RESULTS: The study revealed that GLS is widely expressed in immune cells and is closely linked to the complex immune cell interactions within periodontal tissues. This finding underscores GLS as a potential therapeutic target in the context of periodontitis, associated with cuproptosis. The integration of single-cell sequencing data highlighted the significant role of cuproptosis in the diversity and complexity of periodontitis pathogenesis. CONCLUSION: This research advances the understanding of the crosstalk between periodontitis and cuproptosis, emphasising the role of CRGs, especially GLS, in periodontitis. Furthermore, this study on cuproptosis may contribute to future diagnostic and therapeutic strategies for periodontitis.