Shared Senescence-associated Gene Networks in PCOS and T2DM: Biomarker Identification and Functional Validation

Mingyue Kong¹Kun Lou²Dan Liu³Ziqi Dai⁴Tianjiao Li⁴Yihan Yang⁴Xuesong Zhang⁵Xin Chen^5*

• ¹College of Traditional Chinese Medicine,Changchun University Of Chinese Medicine, Changchun, China
• ²Changchun Orthopaedics Hospital, Changchun, China
• ³Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
• ⁴Changchun University of Chinese Medicine, Changchun, China
• ⁵Gynecology Department, Affliated Hospital of Changchun University of Chinese Medicine, Changchun, China

(1) Background: Polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) are two prevalent and interrelated disorders that pose an increasingly significant global health burden. Cellular senescence may represent a pivotal process driving the progression of both conditions. Senescent cells, through the senescence-associated secretory phenotype (SASP), can induce chronic inflammation, which is highly likely to exacerbate the pathological progression of PCOS and T2DM. However, the molecular pathways linking cellular senescence to PCOS and T2DM have not yet been systematically elucidated. (2) Methods The transcriptome datasets of PCOS (GSE54248) and T2DM (GSE23561) were obtained from the GEO database, and differentially expressed genes (DEGs) were screened using the limma package. Age-related DEGs (ARDEGs) were obtained by intersecting DEGs with age-related genes, and the protein-protein interaction (PPI) network was constructed based on the STRING database. Hub genes with diagnostic value were determined via the Wilcoxon rank sum test and receiver operating characteristic (ROC) curve. CIBERSORT was used to analyze the infiltration characteristics of immune cells, and the functions of the hub gene were analyzed by gene set enrichment analysis (GSEA). Single-cell sequencing was used to locate gene expression patterns, and qRT‒PCR was used to verify the expression of candidate genes in clinical samples. (3) Results: 80 DEGs between PCOS and T2DM samples were obtained, and 15 ARDEGs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they were related to inflammatory response and immune response, and were involved in specific functions and pathways. Four hub genes were identified: TUBA4A, RTN1, G6PD, and HP. qRT‒PCR experimental results showed that HP, G6PD, TUBA4A, and RTN1 were highly expressed in the peripheral blood of PCOS and T2DM patients, compared to healthy people. (4) This study revealed the potential connections between PCOS, T2DM, and aging-related molecular networks and signaling pathways and discovered multiple potential therapeutic targets. It provides new intervention directions for clinicians, especially based on aging mechanisms.