Over-expression of Wilms' tumor 1-associating Protein Promotes Tumorigenesis and Predicts Poor Prognosis in Endometrial Cancer
Abstract Background. Wilms’ tumor 1‐associating protein (WTAP) was previously reported to play critical roles in the tumorigenesis of different malignancies, and its expression level has been linked to a poor prognosis of several cancers. We evaluated the role of WTAP in endometrial carcinoma (EC) using publicly available data from The Cancer Genome Atlas (TCGA). Methods. The relationship between WTAP expression and clinical characteristics was assessed with the Wilcoxon signed‐rank test and logistic regression. Clinical factors associated with prognosis were evaluated using Cox regression analysis and Kaplan-Meier method. Gene set enrichment analysis (GSEA) was conducted using TCGA dataset. Results. Our results revealed that WTAP was significantly up-regulated in EC. Increased WTAP expression in EC was significantly associated with high-grade tumor (odds ratio [OR] = 2.126) and high-risk histology (OR = 1.915) (all P < 0.05). Patients with high WTAP expression had a worse overall survival (OS) (hazard ratio [HR] = 2.868, 95% confidence interval [CI] = 1.259-6.532; P = 0.0087) and recurrence-free survival (RFS) (HR =3.148, 95% CI = 1.372-7.220; P = 0.004) than those with low WTAP expression. Multivariate analysis showed that WTAP expression remained an independent predictor of OS and RFS. Furthermore, GSEA showed that wnt/β-catenin signaling pathway was differentially enriched in WTAP high expression phenotype. Conclusions. WTAP was over-expressed in EC. WTAP expression was an independent predictor of poor OS and RFS in EC, and it was associated with advanced grade, high-risk EC. Moreover, the wnt/β-catenin signaling pathway might be the key process regulated by WTAP in EC.