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Expression Of Tfeb In Epithelial Ovarian Cancer And Its Role In Autophagy

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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摘要
The transcription factor EB (TFEB), as a master gene for autophagy, regulates expression of many genes encoding lysosomal enzymes and membrane proteins. In this study, expression level of TFEB in ovarian cancer and its correlations with clinicopathological variables and autophagy were investigated. First immunohistological staining was utilized to evaluate TFEB expression in cancer and pericarcinous tissues of 242 patients with ovarian epithelial cancer. The correlations of TFEB expression with clinicopathological features, especially with lysosomal associated proteins expression were analyzed, and the effect of TFEB on prognosis of ovarian cancer patients was studied by Kaplan-Meier analysis and Cox proportional hazard modeling. In addition, vitro experiments were performed through shTFEB. The results showed that TFEB was significantly higher expressed in ovarian epithelial cancer, and there were significantly positive correlations between TFEB expression and lysosomal associated proteins Beclin1, cathepsin D and cathepsin L (all P<0.01). Furth more, TFEB correlated significantly with clinical stage, pathological grade and metastases, and the patients with higher TFEB expression often showed poor survival (P<0.001). Functionally, depletion of TFEB by shRNA inhibited cell proliferation, cell migration, and autophagy induced by starvation in ovarian cancer cell line. TFEB expression correlated with autophagy and aggressive clinical features in ovarian cancer, and higher TFEB expression was an independent prognostic factor for ovarian cancer.
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关键词
TFEB, ovarian cancer, prognostic factor, autophagy
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