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血管内皮生长抑制剂,一种肿瘤坏死因子家族的细胞因子,与肾细胞癌的上皮-间质转化相关。

Vascular Endothelial Growth Inhibitor, a Cytokine of the Tumor Necrosis Factor Family, is Associated With Epithelial-Mesenchymal Transition in Renal Cell Carcinoma.

作者信息

Zhao Qiang, Liu Tiezhu, Hong Baoan, Wang Feng, Zhou Changhua, Du Xin, Chen Siqi, Deng Xiaohu, Duoerkun Shayiremu, Li Qing, Yang Yong, Gong Kan, Zhang Ning

机构信息

Department of Urology, Peking University Cancer Hospital, Beijing Institute for Cancer Research.

Department of Urology, Daqing Oilfield General Hospital, Heilongjiang.

出版信息

Appl Immunohistochem Mol Morphol. 2018 Nov/Dec;26(10):727-733. doi: 10.1097/PAI.0000000000000517.

Abstract

Previous studies have revealed that the activation of the epithelial-mesenchymal transition (EMT) endows metastatic properties upon cancer cells to promote invasion and migration. In this study, immunohistochemical analysis was performed in 50 cases of clear cell renal cell carcinoma (RCC) and paired normal kidney tissues. We detected the expression of vascular endothelial growth inhibitor (VEGI) and EMT markers (E-cadherin, fibronectin, and Slug) and recorded the clinical, pathologic, and follow-up (median follow-up: 79.0 mo) information. The expression of VEGI and E-cadherin was significantly lower in RCC tissues compared with normal kidney tissues (P<0.001). However, the expression of fibronectin and Slug was higher in RCC tissues (P<0.05). VEGI and EMT marker expression marginally differed in tumor size and stage. Significant differences were found in the pathologic grade (P<0.05). The Spearman correlation analysis suggested a positive correlation between VEGI and E-cadherin (r=0.451, P<0.01). A negative correlation was shown between VEGI and fibronectin (r=-0.465, P<0.01). There was also a negative correlation between VEGI and Slug (r=-0.758, P<0.01). During the 79.0 months (range, 7 to 119 mo) of follow-up, 6 patients died due to RCC, and the tumor-free survival rate was 88% (44/50). We did not find a significant correlation between VEGI/EMT markers (E-cadherin, fibronectin, and Slug) and overall survival (P>0.05). Our findings indicate that VEGI plays an important role in EMT in RCC. It suggests that VEGI may be investigated as a disease biomarker and therapeutic target in RCC.

摘要

既往研究表明,上皮-间质转化(EMT)的激活赋予癌细胞转移特性,以促进侵袭和迁移。在本研究中,对50例透明细胞肾细胞癌(RCC)及配对的正常肾组织进行了免疫组化分析。我们检测了血管内皮生长抑制因子(VEGI)和EMT标志物(E-钙黏蛋白、纤连蛋白和Slug)的表达,并记录了临床、病理及随访(中位随访时间:79.0个月)信息。与正常肾组织相比,RCC组织中VEGI和E-钙黏蛋白的表达显著降低(P<0.001)。然而,RCC组织中纤连蛋白和Slug的表达较高(P<0.05)。VEGI和EMT标志物的表达在肿瘤大小和分期方面差异不明显。在病理分级方面存在显著差异(P<0.05)。Spearman相关性分析表明,VEGI与E-钙黏蛋白呈正相关(r=0.451,P<0.01)。VEGI与纤连蛋白呈负相关(r=-0.465,P<0.01)。VEGI与Slug之间也呈负相关(r=-0.758,P<0.01)。在79.0个月(范围:7至119个月)的随访期间,6例患者死于RCC,无瘤生存率为88%(44/50)。我们未发现VEGI/EMT标志物(E-钙黏蛋白、纤连蛋白和Slug)与总生存率之间存在显著相关性(P>0.05)。我们的研究结果表明,VEGI在RCC的EMT过程中起重要作用。这表明VEGI可能作为RCC的疾病生物标志物和治疗靶点进行研究。

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