WT1和SPRY2在上皮性卵巢癌中的作用研究

The study on the role of WT1 and SPRY2 in epithelial ovarian cancer

为探讨肾母细胞瘤(WT1)基因和信号通路特异性抑制蛋白(SPRY2)在上皮性卵巢癌(EOC)中的临床意义,通过qRT-PCR和Western blot检测WT1与SPRY2的表达,分析两者与EOC患者临床病理特征及复发的关系;分析两者之间的相关性;通过体外细胞试验初探两者在EOC细胞侵袭中的作用机制。结果表明:EOC原发灶中WT1呈高表达,SPRY2呈低表达,两者与临床FIGO分期、病理分级及复发率密切相关;与原发灶相比,EOC转移灶中WT1表达水平进一步升高,SPRY2表达水平进一步降低;原发灶和转移灶中WT1与SPRY2的表达均呈负相关;WT1敲减后EOC细胞株SKOV3细胞的侵袭能力减弱,SPRY2表达明显上调,ERK1/2磷酸化明显受到抑制。WT1和SPRY2表达与EOC发生发展密切相关,可作为EOC恶性程度及不良预后的评价指标,WT1可能通过下调SPRY2进而调控ERK1/2信号通路促进EOC细胞的侵袭转移。

To investigate the expression and clinical significance of WT1 and SPRY2 in epithelial ovarian cancer(EOC),qRT-PCR and Western blot were used to examine the expression of WT1 and SPRY2,analyze their relationships with clinicopathological characteristics and recurrence of EOC patients,and explore the correlation between WT1 and SPRY2.Moreover,the underlying mechanisms of WT1 and SPRY2 in EOC were verified.The expression of WT1 was up-regulated,but the expression of SPRY2 was down-regulated in EOC primary tumor tissues,which were both closely associated with clinical FIGO stage,pathology grade and recurrence rate.Compared with primary tumor tissues,the expression of WT1 was further higher and the level of SPRY2 was further lower in metastatic tumor tissues.The expression of WT1 was negatively correlated with SPRY2 in both primary and metastatic tumor tissues.In cultured cells models,WT1 depletion significantly suppressed SKOV3 cell invasion,promoted SPRY2 expression and inhibited ERK1/2 phosphorylation.The expressions of WT1 and SPRY2 were closely related with the process of EOC,which may act as indicators for the degree of malignancy and poor prognosis of EOC.WT1 may promote the invasion and metastasis of EOC cells by reducing SPRY2 expression and activating ERK1/2 signaling.