Decreased expression of TFAP2B in endometrial cancer predicts poor prognosis: A study based on TCGA data.

BACKGROUND:Transcription factor activator protein-2β (TFAP-2β) was previously reported to constituted promoter activity in endometrial carcinoma (EC). We evaluated the role of TFAP2B in ECs using publicly available data from The Cancer Genome Atlas (TCGA). METHODS:The relationship between clinical pathologic features and TFAP2B were analyzed with the Wilcoxon signed-rank test and logistic regression. Clinicopathologic characteristics associated with overall survival in TCGA patients using Cox regression and the Kaplan-Meier method. Gene Set (GSEA) was performed using TCGA data set. RESULTS:Reduced TFAP2B expression in EC was significantly associated with high grade (OR=2.2 for well, moderate vs. poor), stage (OR=2.5 for I vs. IV), histology (OR=1.8 for serous vs. endometrioid), distant metastasis (OR=2.4 for positive vs. negative) (all p-values<0.05). Kaplan-Meier survival analysis showed that EC with TFAP2B-low had a worse prognosis than that with TFAP2B-high (p=0.013). The univariate analysis revealed that TFAP2B-low correlated significantly with a poor overall survival (OS) (HR: 2.35; 95% confidence interval [CI]: 1.17-4.73; p=0.016). The multivariate analysis revealed that TFAP2B remained independently associated with overall survival, with a HR of 4.42 (CI: 1.25-12.64; p=0.021). GSEA show that p53/hypoxia pathway, androgen response, notch signaling, fatty acid metabolism, glycolysis and estrogen response late are differentially enriched in TFAP2B high expression phenotype. CONCLUSIONS:TFAP2B expression may be a potential prognostic molecular marker of poor survival in endometrial cancer, Moreover, the p53/hypoxia, androgen response and notch signaling pathway may be the key pathway regulated by TFAP2B in EC.

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