Wang Tianmei, Chen Xin, Li Cong
Department of Gynecology, First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400016, P.R. China.
Department of Gynecology and Obstetrics, The 958th Army Hospital of the Chinese People'S Liberation Army, Jiangbei District, Chongqing, 400000, P.R. China.
J Ovarian Res. 2025 Mar 5;18(1):42. doi: 10.1186/s13048-025-01637-y.
The pathogenesis of polycystic ovary syndrome (PCOS) is still unknown, so finding the molecular mechanisms of pathogenesis is crucial in PCOS.
The GSE34526 dataset from the Gene Expression Omnibus (GEO) database was used to screen biomarkers in this study. KEGG enrichment analysis of GSE34526 was performed using Gene Set Enrichment Analysis (GSEA). The differentially expressed genes(DEGs) were screened and analyzed for lysosome-related genes. Subsequently, further KEGG and GO analyses were performed, and it was found that it was enriched in the ferroptosis pathway, and then the ferroptosis-related differential genes were obtained. The genes at the core position were obtained by the Protein-Protein Interaction(PPI) network. We then focused our attention on SRC and verified the differential expression of SRC in ovarian tissues of hyperandrogenemic, hyperlipemic and control groups, as well as the differences in conception rate and litter rate of each group by rat test.
GSEA analysis of the gene dataset GSE34526 revealed that LYSOSOME was significantly enriched in the PCOS group. There were 188 lysosome-related differentially expressed genes(LRDEGs) in granulosa cells from patients with PCOS, and 41 ferroptosis-related differentially expressed genes(FRDEGs). It was found that six of these genes, SRC, NCF2, SLC2A8, FTL, SLC2A6, SLC3A2, were present in all three datasets. SRC was the top ranked gene in the PPI network of FRDEGs.As verified by the rat model, the expression of SRC in the ovarian tissues of the hyperandrogenemic group was significantly higher than that of the control group (P=0.004) and the hyperlipemic group (P=0.002).
SRC, as an important gene involved in lysosomal function and regulating ferroptosis, is expected to be a potential target for PCOS.
多囊卵巢综合征（PCOS）的发病机制仍不清楚，因此找到其发病的分子机制对PCOS至关重要。
本研究使用来自基因表达综合数据库（GEO）的GSE34526数据集筛选生物标志物。使用基因集富集分析（GSEA）对GSE34526进行KEGG富集分析。筛选差异表达基因（DEG）并分析与溶酶体相关的基因。随后，进行进一步的KEGG和GO分析，发现其在铁死亡途径中富集，进而获得与铁死亡相关的差异基因。通过蛋白质-蛋白质相互作用（PPI）网络获得核心位置的基因。然后我们将注意力集中在SRC上，并通过大鼠实验验证了SRC在高雄激素血症组、高脂血症组和对照组卵巢组织中的差异表达，以及各组受孕率和产仔率的差异。
对基因数据集GSE34526的GSEA分析显示，溶酶体在PCOS组中显著富集。PCOS患者颗粒细胞中有188个与溶酶体相关的差异表达基因（LRDEG），以及41个与铁死亡相关的差异表达基因（FRDEG）。发现其中6个基因，即SRC、NCF2、SLC2A8、FTL、SLC2A6、SLC3A2，在所有三个数据集中均存在。SRC是FRDEG的PPI网络中排名第一的基因。经大鼠模型验证，高雄激素血症组卵巢组织中SRC的表达明显高于对照组（P=0.004）和高脂血症组（P=0.002）。
SRC作为参与溶酶体功能并调节铁死亡的重要基因，有望成为PCOS的潜在靶点。
