Molecular Signatures of Localized Clear Cell Renal Cell Carcinoma to Predict Disease-Free Survival after Nephrectomy
Molecular Signatures of Localized Clear Cell Renal Cell Carcinoma to Predict Disease-Free Survival after Nephrectomy
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DOI：
10.1158/1055-9965.epi-08-0786
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发表时间：
2009-03-01
影响因子：
3.8
通讯作者：
Belldegrun, Arie S.
中科院分区：
文献类型：
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作者：
Klatte, Tobias;Seligson, David B.;Belldegrun, Arie S.
目的：为了确定局部（NOMO）透明细胞肾细胞癌（RCC）的分子特征，并评估其预测outcome.Methods的能力：170例接受肾切除术的局部透明细胞RCC患者的临床特征和病理记录进行了审查。使用肾癌相关的蛋白质标记物组对所有原发性肿瘤的组织微阵列进行免疫组织化学分析，所述蛋白质标记物组包括CAIX、CAXII、CXCR 3、凝溶胶蛋白、Ki-67、波形蛋白、EpCAM、p21、p27、p53、pS 6、PTEN、HIF-1 α、pAkt、VEGF-A、VEGF-C、VEGF-D、VEGFR-1、VEGFR-2和VEGFR-3。与无病生存期（DFS）的协会进行了评估与考克斯模型，和一致性指数评估预后accuracy.Results：中位随访时间为7.1年。最终的多变量考克斯模型确定T分类、东部肿瘤协作组体力状态和5种分子标志物（Ki-67、p53、内皮细胞VEGFR-1、上皮细胞VEGFR-1和上皮细胞VEGF-D）是DFS的独立预后指标。基于这些标记物的分子特征预测DFS的准确度为0.838，比T分类提高了0.746，加州大学洛杉矶分校综合分期系统为0.780。结论：由Ki-67、p53、内皮细胞VEGFR-1、上皮细胞VEGFR-1和上皮细胞VEGF-D 5种分子标志物组成的分子标志物可预测局限性透明细胞肾细胞癌的无病期。特征和列线图的预后能力可能上级单独的临床和病理因素，并且可以识别具有攻击性临床行为的局部患者的子集。需要对列线图进行独立的外部验证。（癌症流行病学生物标志物Prev 2009;18（3）：894-900）
Purpose: To identify the molecular signature of localized (NOMO) clear cell renal cell carcinoma (RCC) and assess its ability to predict outcome.Methods: Clinical characteristics and pathologic records of 170 patients with localized clear cell RCC who underwent nephrectomy were reviewed. Immunohistochemical analysis was done on a tissue microarray of all primary tumors using a kidney cancer-related panel of protein markers, which included CAIX, CAXII, CXCR3, gelsolin, Ki-67, vimentin, EpCAM, p21, p27, p53, pS6, PTEN, HIF-1 alpha, pAkt, VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2, and VEGFR-3. Associations with disease-free survival (DFS) were evaluated with Cox models, and a concordance index assessed prognostic accuracy.Results: Median follow-up was 7.1 years. The final multivariate Cox model determined T classification, Eastern Cooperative Oncology Group performance status, and five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) to be independent prognostic indicators of DFS. The molecular signature based on these markers predicted DFS with an accuracy of 0.838, an improvement over T classification of 0.746, and the University of Califomia-Los Angeles Integrated Staging System of 0.780. A constructed nomogram combined the molecular, clinical, and pathologic factors and approached a concordance index of 0.904.Conclusions: A molecular signature consisting of five molecular markers (Ki-67, p53, endothelial VEGFR-1, epithelial VEGFR-1, and epithelial VEGF-D) can predict DFS for localized clear cell RCC. The prognostic ability of the signature and nomogram may be superior to clinical and pathologic factors alone and may identify a subset of localized patients with aggressive clinical behavior. Independent, external validation of the nomogram is required. (Cancer Epidemiol Biomarkers Prev 2009;18(3):894-900)