Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma
Prospective analysis of circulating endostatin levels in patients with renal cell carcinoma
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DOI：
10.1002/cncr.10845
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发表时间：
2002-10-15
期刊：
影响因子：
6.2
通讯作者：
Libutti, SK
中科院分区：
文献类型：
--
作者：
Feldman, AL;Alexander, HR;Libutti, SK
背景资料。本研究的目的是评估肾癌患者内源性内皮抑素的循环水平，并确定这些水平与循环血管内皮生长因子(VEGF)水平和预后的关系。方法：作者前瞻性地研究了66例患者(男性48例，女性18例；平均年龄50岁)，在国家癌症研究所进行了肾切除治疗肾癌的临床试验。在66例患者中，有51例(77%)在切除肾时出现了转移。用竞争性酶免疫分析法检测手术前和术后的血清内皮抑素和血管内皮生长因子水平，并与32名年龄和性别匹配的健康对照组进行比较。结果：肾癌患者术前内皮抑素水平高于健康对照组(P=0.05)。治疗前血清内皮抑素水平与血清血管内皮生长因子水平呈弱至中度相关(r=0.47P=0.001)，肾切除后两者水平均显著升高(P<；0.0001和P<；0.0001；n=41)。此外，肾切除术后内皮抑素水平升高两倍以上的患者的预后明显比未升高的患者差(P=0.018)。当排除无转移的患者时，这种关联更加明显(P=0.0037)。结论：肾癌患者循环内皮抑素水平升高，且与循环血管内皮生长因子水平相关。肾切除后内皮抑素水平升高，升高幅度最大的患者生存时间缩短。这些发现表明肾癌患者的肿瘤侵袭性和内源性内皮抑素的产生之间存在关联。
BACKGROUND. The aim of the current study was to assess circulating levels of endogenous endostatin in patients with renal carinoma and to determine the relationship of these levels to circulating levels of vascular endothelial growth factor (VEGF) and prognosis.METHODS. The authors prospectively studied 66 patients (48 male, 18 female; mean age, 50 years) undergoing nephrectomy for renal carcinoma oil clinical trials at the National Cancer Institute. Metastases were present in 51 of 66 patients (77%) at the time of nephrectomy. Preoperative and followup serum endostatin and VEGF levels were determined using competitive enzyme immunoassays and compared to a group of 32 age- and gender-matched healthy controls. Associations between circulating endostatin levels and clinicopathologic variables, including survival, were determined.RESULTS. Preoperative endostatin levels were higher in renal carcinoma patients than in healthy controls (P = 0.05). There was a weak to moderate correlation between pretreatment serum endostatin levels and serum VEGF levels (r = 0.47; P = 0.001), and levels of both proteins increased significantly following nephrectomy (P < 0.0001 and P < 0.0001, respectively; n = 41). In addition, patients whose endostatin levels increased more than twofold after nephrectomy had significantly poorer prognoses than patients without such an increase (P = 0.018). This association was more pronounced when patients without metastases were excluded (P = 0.0037).CONCLUSIONS. Circulating endostatin levels are elevated in patients with renal carcinoma and correlate with circulating VEGF levels. Endostatin levels increase after nephrectomy, and patients with the greatest increases experience shortened survival times. These findings suggest an association between tumor aggressiveness and the production of endogenous endostatin in patients with renal carcinoma.