Activation and DNA methylation of PANoptosis in polycystic ovary syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disorder involving various pathophysiological factors and is currently incurable. This study aimed to explore the potential role of pan-apoptosis in PCOS. METHODS: Differentially expressed genes (DEGs) between PCOS and healthy controls were identified in GSE155489 and GSE10946, and enrichment analysis was performed. The activation of PANoptosis in PCOS was evaluated, PANoptosis-related DEGs were screened, and the receiver operating characteristic (ROC) curve was plotted. The methylation modification of PANoptosis-related DEGs were assessed from differentially methylated probes in GSE80468 dataset. Protein expression was detected using Western blot, and DNA methylation levels were measured using PCR in PCOS patients and healthy controls. RESULTS: PANoptosis was significantly activated in PCOS. The intersection DEGs in GSE155489 and GSE10946 datasets significantly participated in signaling pathways such as Cell adhesion molecules, B cell receptor signaling pathway, and Rap1 signaling pathway. TNFSF10, IL-18, and CASP2 were differentially expressed in PCOS and may be subject to methylation modification, with the ROC curve suggesting they have diagnostic roles in PCOS. Experimental detection confirmed that TNFSF10 is hypomethylated and highly expressed in PCOS, while CASP2 is hypermethylated and lowly expressed in PCOS. CONCLUSION: Through comprehensive analysis of gene expression and DNA methylation data, this study revealed the correlation between PCOS and PANoptosis, providing new insights into the molecular basis of PCOS and offering potential biomarkers for the development of future diagnostic and therapeutic strategies.