Zhu Shibo, Liu Guochang, Fu Wen, Hu Jinhua, Fu Kai, Jia Wei
Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, People's Republic of China.
Onco Targets Ther. 2017 Feb 16;10:955-963. doi: 10.2147/OTT.S127419. eCollection 2017.
Overexpression of has been reported in many tumors, where it promotes tumorigenesis and progression, as well as correlates with the prognosis of different malignancies. However, expression and its function have rarely been reported in Wilms' tumor (WT). This study aimed to reveal the clinical significance of expression in patients with WT and determine its mechanisms.
We analyzed the expression of and its correlations with various clinicopathological features in 72 WT tissues and 72 adjacent non-cancerous tissues by immunohistochemistry. Cox proportional hazards regression models were used to investigate the correlations between expression and the prognosis of WT patients. Fresh frozen samples from 20 WT patients were examined using Western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). In WT cell line, after knockdown by sh- and growth arrest-specific 6 (Gas6) stimulation, the cell proliferation, migration and invasion abilities were detected by methyl-thiazolyl-tetrazolium (MTT), clone-forming, wound-healing and transwell assays. Meanwhile, the tumor-forming ability was tested on nude mice xenograft models. Finally, the expression of several proteins in signal pathways was quantified by WB assays.
Compared with the adjacent non-cancerous tissues, the expression of was significantly higher in WT tissues (<0.05). High expression of was associated with tumor recurrence or lung metastasis of WT patients and was a prognostic factor for WT patients (<0.05). In vitro assays, the proliferation, migration and invasion of WT cells decreased with knockdown and significantly increased with activation by Gas6 (<0.05). In vivo assays, the ability of tumorigenicity in WT cells reduced dramatically after knockout (<0.05). Moreover, - pathway proteins decreased with knockdown.
Our results suggest that is highly expressed in WT and is a prognostic factor, which could promote the progression of WT in vitro and in vivo. It may also be a potential biomarker for WT.
已有报道称[具体物质名称]在许多肿瘤中过表达，它促进肿瘤发生和进展，并与不同恶性肿瘤的预后相关。然而，[具体物质名称]在肾母细胞瘤（WT）中的表达及其功能鲜有报道。本研究旨在揭示[具体物质名称]在WT患者中的临床意义并确定其机制。
我们通过免疫组织化学分析了72例WT组织和72例相邻非癌组织中[具体物质名称]的表达及其与各种临床病理特征的相关性。采用Cox比例风险回归模型研究[具体物质名称]表达与WT患者预后的相关性。使用蛋白质免疫印迹法（WB）和实时定量聚合酶链反应（RT-qPCR）检测了20例WT患者的新鲜冰冻样本。在WT细胞系中，通过短发夹RNA（sh-）敲低[具体物质名称]并经生长停滞特异性蛋白6（Gas6）刺激后，采用甲基噻唑基四氮唑（MTT）法、克隆形成法、伤口愈合法和Transwell法检测细胞增殖、迁移和侵袭能力。同时，在裸鼠异种移植模型上测试肿瘤形成能力。最后，通过WB法对信号通路中几种蛋白质的表达进行定量分析。
与相邻非癌组织相比，WT组织中[具体物质名称]的表达显著更高（<0.05）。[具体物质名称]的高表达与WT患者的肿瘤复发或肺转移相关，并且是WT患者的预后因素（<0.05）。在体外实验中，WT细胞的增殖、迁移和侵袭能力随着[具体物质名称]的敲低而降低，并随着Gas6激活[具体物质名称]而显著增加（<0.05）。在体内实验中，[具体物质名称]敲除后WT细胞的肿瘤形成能力显著降低（<0.05）。此外，随着[具体物质名称]的敲低，[具体信号通路名称] - 通路蛋白减少。
我们的结果表明，[具体物质名称]在WT中高表达且是一个预后因素，它可在体外和体内促进WT的进展。它也可能是WT的一个潜在生物标志物。
