Expression and significance of B7-H3 and Tie-2 in the tumor vasculature of clear cell renal carcinoma.
Expression and significance of B7-H3 and Tie-2 in the tumor vasculature of clear cell renal carcinoma.
复制标题
B7-H3和Tie-2在透明细胞肾癌肿瘤血管中的表达及意义
DOI：
10.2147/ott.s147041
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发表时间：
2017
影响因子：
4
通讯作者：
Hou J
中科院分区：
文献类型：
--
作者：
Zhang X;Ji J;Zhang G;Fang C;Jiang F;Ma S;Hou J
肿瘤血管生成是肿瘤生长和转移所必需的，Ang/Tie-2轴在血管生成中起着关键作用。B7- h3是共刺激分子B7家族的新成员，在t细胞介导的抗肿瘤免疫应答中具有重要作用，肿瘤B7- h3异常表达常与不良预后相关。然而，B7-H3与透明细胞肾癌（ccRCC）血管生成的关系尚不清楚。本研究采用免疫组织化学方法检测82例ccRCC患者组织芯片中B7-H3和Tie-2的肿瘤血管表达。结果显示，B7-H3在ccRCC的肿瘤血管内皮中高表达，并与ccRCC的分级和肿瘤淋巴结转移（TNM）分期相关。虽然血管Tie-2表达也与T分期和淋巴结转移相关，但与ccRCC分级或远处转移无关。CD34标记的微血管密度（MVD）与肿瘤分级和TNM分期相关。B7-H3、Tie-2的表达与MVD呈正相关，且与MVD呈正相关。免疫荧光染色显示B7-H3和Tie-2在ccRCC血管内皮中共表达。综上所述，我们的研究结果表明B7-H3和Tie-2在ccRCC肿瘤血管中的表达与疾病的进展和预后密切相关。此外，B7-H3可能通过Tie-2途径促进ccRCC血管生成。因此，B7-H3可能作为ccRCC预后的有效内皮标志物，成为ccRCC抗血管生成靶向治疗的有希望的靶点。
Tumor angiogenesis is required for tumor growth and metastasis, and the Ang/Tie-2 axis plays a pivotal role in angiogenesis. B7-H3, a new member of the B7 family of costimulatory molecules, has a critical function in the T-cell-mediated antitumor immune response, and abnormal tumor B7-H3 expression is frequently associated with a poor prognosis. However, the relationship between B7-H3 and angiogenesis in clear cell renal carcinoma (ccRCC) remains unclear. In this study, we used immunohistochemical methods to detect tumor vascular expression of B7-H3 and Tie-2 in tissue microarrays of 82 ccRCC patient samples. According to the results, B7-H3 is highly expressed in the tumor vascular endothelium of ccRCC and is associated with the ccRCC grade and tumor-node-metastasis (TNM) stage. Although vascular Tie-2 expression was also correlated with T stage and lymph node metastasis, it was not related to ccRCC grade or distant metastasis. The microvessel density (MVD) labeled by CD34 was correlated with tumor grade and TNM stage. Expression of B7-H3 and Tie-2 was positively correlated, and the levels were positively associated with the MVD. Additionally, immunofluorescence staining revealed coexpression of B7-H3 and Tie-2 in the vascular endothelia of ccRCC. Collectively, our findings suggest that expression of B7-H3 and Tie-2 in ccRCC tumor vasculature is closely related to the progression and prognosis of the disease. Furthermore, B7-H3 possibly promotes ccRCC angiogenesis through the Tie-2 pathway. Thus, B7-H3 might serve as an effective endothelial marker for ccRCC prognosis and become a promising target for ccRCC anti-angiogenic-targeted therapy.