Abstract: bjective To identify the drivers of ovarian cancer metastasis by analyzing gene expression profiles of primary ovarian carcinomas and their corresponding omental metastases. Furthermore, it aims to explore the biological functions and potential regulatory mechanisms of these drivers. Methods Differential expression analyses were performed on paired datasets obtained from the Gene Expression Omnibus (GEO)，specifically GSE178913 and GSE222982，to identify common differentially expressed genes (DEGs), followed by pathway enrichment analysis. Candidate genes were subsequently assessed in cohorts from The Cancer Genome Atlas (TCGA)  for expression patterns and prognostic significance. The expression of the cluster of differentiation 36 (CD36) protein in paired primary and metastatic lesions was validated by immunohistochemistry. Functional studies were employed by CD36 silencing in A2780 cells and overexpressing in OVCAR⁃3 cells via plasmid transfection or lentiviral transduction. Cell migration and invasion were evaluated using wound healing and Transwell assays. Co⁃expression analysis, protein⁃protein interaction network construction, and transcription factor prediction collectively suggested an association between signal transducer and activator of transcription 3 (STAT3) signaling activity and CD36 expression. This association was further explored in vitro and in a mouse model of ovarian cancer peritoneal dissemination using the STAT3 inhibitor Stattic, with CD36 re⁃expression to assess whether metastasis⁃related phenotypes could be partially rescued. Results The common DEGs in primary ovarian tumors and matched omental metastases were significantly enriched in lipid metabolism⁃related pathways, particularly the PPAR signaling pathway. Within this pathway, the key fatty acid transporter CD36 was significantly upregulated in metastatic lesions and advanced⁃stage disease (P<0.05). Analyses of  TCGA data revealed that high CD36 expression independently predicted poor prognosis (HR=2.066, 95%CI: 1.414-3.035, P<0.001). Immunohistochemistry further confirmed higher CD36 protein levels in metastatic lesions relative to primary tumors. Functionally, CD36 knockdown markedly suppressed migration and invasion in A2780 cells (both P<0.01), whereas CD36 overexpression enhanced these phenotypes in OVCAR⁃3 cells (both P<0.05). STAT3 might be an upstream regulator of CD36. In A2780 cells, pharmacologic STAT3 inhibition with Stattic reduced CD36 expression and decreased migration/invasion (all P<0.01), and CD36 re⁃expression partially rescued these effects (all P<0.01). In vivo, STAT3 inhibition significantly reduced peritoneal metastatic nodule burden and ascites formation (both P<0.05). Conclusions CD36 potentially functions as a metastasis⁃promoting factor in ovarian cancer. Its expression  is upregulated in metastatic and advanced⁃stage disease，serving as an independent predictor of poor prognosis，and enhances the migration and invasion capabilities of ovarian cancer cells. Furthermore, STAT3 signaling activity is associated with CD36 expression and metastasis⁃related phenotypes. The STAT3/CD36⁃associated pathway may represent a potential therapeutic target, and CD36 may serve as a candidate biomarker for metastatic risk and adverse outcomes.

Key words: Ovarian Cancer, Metastasis, Lipid Metabolism, Cluster of differentiation 36, Signal transducer and activator of transcription 3