Hongrong Wu1, Jian Zhang2. 1. Department of pathology, The Xiang Ya Hospital of Central South University, Changsha, Hunan Province, China. 2. Department of pathology, The Xiang Ya Hospital of Central South University, Changsha, Hunan Province, China. Electronic address: 1478115560@qq.com.
Abstract
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 Enrichment Analysis (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.
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 Enrichment Analysis (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.