CXCL12 promotes EMT-mediated malignant transformation of endometriosis-associated ovarian cancer via PI3K/Akt signaling: an integrated transcriptomic and clinical study

BACKGROUND: Endometriosis-associated ovarian cancer is a distinct form of epithelial ovarian cancer that arises from the malignant transformation of benign endometriotic lesions. While epithelial-mesenchymal transition is acknowledged as a crucial process in the progression of endometriosis-associated ovarian cancer, the upstream regulatory mechanisms and key molecular drivers are not fully understood. METHODS: Differentially expressed genes between benign endometriosis and endometriosis-associated ovarian cancer (EAOC) tissues were identified using Gene Expression Omnibus datasets. The functional role of stromal cell-derived factor-1 (SDF-1) was investigated through in vitro overexpression and knockdown models. Mechanistic studies focused on SDF-1 interaction with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and regulation of epithelial-mesenchymal transition (EMT)-associated proteins. A retrospective analysis of 38 EAOC patients was performed to evaluate the association between SDF-1 expression and prognosis. RESULTS: SDF-1 expression was significantly elevated in EAOC tissues compared with benign endometriosis and correlated with EMT-related phenotypes. Functional assays demonstrated that SDF-1 enhanced cellular migration and invasion capacities. Mechanistically, SDF-1 induced EMT through activation of the PI3K/AKT signaling pathway. Clinically, high SDF-1 expression was associated with reduced overall survival and increased recurrence risk. Multivariate Cox regression analysis identified SDF-1 as an independent adverse prognostic factor in EAOC. CONCLUSIONS: This study systematically elucidates the critical role of SDF-1 in the malignant transformation of endometriosis to EAOC. SDF-1 promotes tumor invasion and metastasis via PI3K/AKT-mediated induction of EMT. These findings highlight SDF-1 as a promising biomarker for early diagnosis and a potential therapeutic target, offering novel avenues for precision management of EAOC.