Background: The inappropriate action of WNT4 and estrogens affects uterine homeostasis and function, and may lead to endometrial cancer (EC). Objective: The aim was to evaluate the alterations ofWNT4gene expression and WNT4 protein immunoreactivity (Ir) in EC, considering tumor characteristics, the clinicopathological association and estrogen dependence. Methods:WNT4mRNA levels were compared between benign (control) endometrium (n= 8) and endometroid EC (EEC) and non-endometroid EC (non-EEC) samples (n= 28) using the real-time PCR technique. The WNT4-Ir and ERα-Ir were evaluated by immunohistochemistry (IHC).WNT4mRNA gene and WNT4-Ir were correlated with clinicopathological and blood morphological parameters. Overall survival (OS) was assessed. The bioanalysis was utilized to study WNT4 expression in large patient cohort (n= 549). Results:WNT4gene expression was decreased in EC samples (specifically in EEC but not in non-EEC) compared to the control. TheWNT4gene expression was also decreased in EC samples categorized by the tumor characteristics. There was no statistical difference in WNT4-Ir or ERα-Ir between the control and EC. There was no correlation between OS andWNT4gene expression and WNT4-Ir. Bioanalysis showed thatWNT4andESR1gene expression alterations tended to be mutually exclusive. An alteration inWNT4expression was found in different histological tumor types in a large group of EC patients. Conclusions: There is a great need to evaluate the molecular background of EC. Our study suggests that theWNT4gene has the potential to be a marker of functional estrogen signaling in EEC.
背景：WNT4与雌激素的不当作用会影响子宫稳态与功能，并可能导致子宫内膜癌（EC）。目的：本研究旨在评估EC中WNT4基因表达及WNT4蛋白免疫反应性（Ir）的变化，并综合考虑肿瘤特征、临床病理关联及雌激素依赖性。方法：采用实时荧光定量PCR技术，比较良性（对照）子宫内膜样本（n=8）与子宫内膜样EC（EEC）及非子宫内膜样EC（non-EEC）样本（n=28）的WNT4 mRNA水平。通过免疫组织化学（IHC）评估WNT4-Ir与ERα-Ir。将WNT4 mRNA基因及WNT4-Ir与临床病理学及血液形态学参数进行相关性分析，并评估总生存期（OS）。利用生物信息学分析技术，对大型患者队列（n=549）中的WNT4表达进行研究。结果：与对照组相比，EC样本（特别是EEC样本，而非non-EEC样本）中WNT4基因表达降低。按肿瘤特征分类的EC样本中，WNT4基因表达同样降低。对照组与EC组之间在WNT4-Ir或ERα-Ir方面无统计学差异。OS与WNT4基因表达及WNT4-Ir之间无相关性。生物信息学分析显示，WNT4与ESR1基因表达变化倾向于互斥。在大型EC患者群体中，不同组织学类型的肿瘤均发现WNT4表达存在改变。结论：亟需评估EC的分子背景。我们的研究表明，WNT4基因有潜力成为EEC中功能性雌激素信号传导的标志物。
WNT4Gene and Protein Expression in Endometrial Cancer and Its Significance
肿瘤(癌症)患者之家