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血管抑肽-1 的低表达与肾细胞癌的临床病理特征相关。

Reduced expression of vasohibin-1 is associated with clinicopathological features in renal cell carcinoma.

机构信息

Tianjin Institute of Urology, Department of Urology, Second Hospital of Tianjin Medical University, no 23, Pingjiang Road, Hexi District, Tianjin, China.

出版信息

Med Oncol. 2012 Dec;29(5):3325-34. doi: 10.1007/s12032-012-0313-x. Epub 2012 Aug 3.

Abstract

Vasohibin-1(VASH1) has recently been isolated as a novel negative feedback inhibitor of angiogenesis. Several studies have demonstrated that VASH1 plays important roles in tumor angiogenesis but the role of this angiogenic inhibitor in renal cell carcinoma (RCC) has not been elucidated until now. In this study, we investigated the expression pattern of VASH1 and the association with clinicopathological features in RCC. Expression of VASH1, hypoxia-inducible factor-1α (HIF-1α), and microvessel density (MVD, labeled by CD34) was assessed by immunohistochemistry in 46 RCC specimens and 20 adjacent nontumorous renal tissues (ANRTs). Correlation between vasohibin-1 and HIF-1α, MVD, and clinicopathological features was then investigated. In RCC, VASH1 was expressed mainly in the cytoplasm and membrane of tumor cells and partly in vascular endothelial cells. In ANRT, it was mainly expressed in the cytoplasm and membrane of renal tubular epithelial cells and partly in vascular endothelial cells and glomerular mesangial cells. The expression level of VASH1 in RCC tissue was significantly lower than that in ANRT and was significantly reduced with the increased degree of malignancy in RCC tissues. In addition, a significantly negative correlation was noted between VASH1 expression and HIF-1α expression and a significantly negative correlation was noted between VASH1 expression and MVD in RCC. Therefore, VASH1 expression is reduced and it associates with clinicopathological features in RCC. Based on our findings and the knowledge of other angiogenesis inhibitors, we postulate that VASH1 would potentially be a biomarker and a candidate for molecular targeted therapy for patients with RCC in the future.

摘要

血管生成抑制因子 1(VASH1)最近被分离出来,是一种新的血管生成负反馈抑制剂。几项研究表明,VASH1 在肿瘤血管生成中发挥着重要作用,但直到现在,这种血管生成抑制剂在肾细胞癌(RCC)中的作用还没有被阐明。在这项研究中,我们研究了 VASH1 的表达模式及其与 RCC 临床病理特征的相关性。通过免疫组织化学方法,在 46 例 RCC 标本和 20 例相邻非肿瘤性肾组织(ANRT)中评估了 VASH1、缺氧诱导因子 1α(HIF-1α)和微血管密度(MVD,用 CD34 标记)的表达。然后研究了 VASH1 与 HIF-1α、MVD 和临床病理特征之间的相关性。在 RCC 中,VASH1 主要在肿瘤细胞的细胞质和细胞膜中表达,部分在血管内皮细胞中表达。在 ANRT 中,它主要在肾小管上皮细胞的细胞质和细胞膜中表达,部分在血管内皮细胞和肾小球系膜细胞中表达。RCC 组织中 VASH1 的表达水平明显低于 ANRT,并且随着 RCC 组织恶性程度的增加而显著降低。此外,在 RCC 中,VASH1 的表达与 HIF-1α的表达呈显著负相关,与 MVD 呈显著负相关。因此,VASH1 的表达在 RCC 中减少,并与临床病理特征相关。基于我们的发现和其他血管生成抑制剂的知识,我们推测 VASH1 可能成为未来 RCC 患者的生物标志物和分子靶向治疗的候选药物。

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