B-317 Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells via integrin αvβ3-PI3K-Akt signaling pathway

Background Patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Therefore, we aimed to screened out stable prognostic markers from platelet-treated ovarian cancer cells, and explored mechanisms by which they promote ovarian cancer metastasis. Methods Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells, and similar studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by analyzing differentially expressed genes (DEGs), protein-protein interaction (PPI) network, Cox proportional hazard models and Kaplan-Meier curves. The expression of TGFBI in the tissue microarray was assessed by immunehistochemical staining (IHC), and its prognostic efficiency was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study. Results TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. Tissue microarray showed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS), and TGFBI was proved to be an independent prognostic factor for ovarian cancer. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3. Conclusions We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway.