Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma
Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma
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DOI：
10.1158/1078-0432.ccr-06-2129
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发表时间：
2007-03-15
影响因子：
11.5
通讯作者：
Kwon, Eugene D.
中科院分区：
文献类型：
--
作者：
Krambeck, Amy E.;Dong, Haidong;Kwon, Eugene D.
目的：肾透明细胞癌是一种免疫原性肿瘤，可在完整的宿主免疫系统存在的情况下进展。我们先前报道，Survivin和137-H1在肾细胞癌中表达时，与疾病进展和死亡独立相关。实验设计：采用免疫组织化学方法检测1990-1994年间298例肾细胞癌患者肾组织中Survivin和137-H1的表达。使用Kaplan-Meier方法估计癌症特异性存活率。用COX比例风险回归模型评估这两个标记物与肾细胞癌死亡的关系。结果：最终，94例患者死于肾细胞癌。在存活的患者中，中位随访期为11.2年(范围0-15年)。Survivin(Low)/B7-H1(-)177例(59.4%)，Hi/137-H1(-)51例(17.1%)，Survivin(Low)/B7-H1(+)29例(9.7%)，Survivin(Hi)/B7-H1(+)41例(13.8%)。每组患者的5年肿瘤特异性生存率分别为89.3%、59.7%、70.0%和16.2%。Survivin(Hi)/B7-H1(+)的联合表达与肾细胞癌死亡呈单变量相关(风险比为12.82；95%可信区间为7.5-21.92；P<；0.001)，多因素分析为(风险比为2.81；95%可信区间为1.5-5.04；P<；0.001)。Survivin(Hi)/B7-H1(+)组与Survivin(Low)/B7-H1(-)组比较，肿瘤组织中单个核细胞和Survivin特异性T细胞水平明显升高。与Survivin(低)/B7-H1(-)肿瘤相比，Survivin(Hi)/B7-H1(+)肿瘤还具有更多的浸润性单个核细胞和Survivin特异性T细胞。综上所述，Survivin和B7-H1的双重表达可用于预测肾细胞癌的侵袭性。
Purpose: Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor that can progress in the presence of an intact host immune system. We previously reported that survivin and 137-H1 are independently associated with disease progression and death when expressed by ccRCC tumors. Herein, we examine the clinical effect of ccRCC combined expression of both survivin and 137-H1.Experimental Design: Specimens from 298 patients who underwent nephrectomy for ccRCC between 1990 and 1994 were immunohistochemically stained for survivin and 137-H1. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of both markers with ccRCC death were assessed using Cox proportional hazards regression models.Results: At last follow-up, 94 patients died from ccRCC. Among the living patients, the median follow-up was 11.2 years (range, 0-15 years). There were 177 (59.4%) survivin(Low)/B7-H1(-), 51 (17.1%) survivin(Hi)/137-H1(-), 29 (9.7%) survivin(Low)/B7-H1(+), and 41 (13.8%) survivin(Hi)/B7-H1(+) tumors. The 5-year cancer-specific survival rates for patients within each group were 89.3%, 59.7%,70.0%, and 16.2%, respectively. Combined survivin(Hi)/B7-H1(+) expression was associated with ccRCC death univariately (risk ratio, 12.82; 95% confidence interval, 7.50-21.92; P < 0.001) and in multivariate analysis (risk ratio, 2.81; 95% confidence interval, 1.56-5.04; P < 0.001). Survivin(Hi)/B7-H1(+) tumors exhibited increased levels of infiltrating mononuclear cells and survivin-specific T cells compared with survivin(Low)/B7-H1(-)tumors.Conclusion: Patients with survivin(Hi)/B7-H1(+) ccRCC tumors are at increased risk of ccRCC death. Survivin(Hi)/B7-H1(+) tumors also harbor increased amounts of infiltrating mononuclear cells and survivin-specific T cells relative to survivin-(Low)/B7-H1(-)tumors. Taken together, dual expression of survivin and B7-H1 can be used to predict ccRCC tumor aggressiveness.