Serum Vascular Endothelial Growth Factor and Fibronectin Predict Clinical Response to High-Dose Interleukin-2 Therapy
Serum Vascular Endothelial Growth Factor and Fibronectin Predict Clinical Response to High-Dose Interleukin-2 Therapy
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DOI：
10.1200/jco.2008.19.1106
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发表时间：
2009-06-01
影响因子：
45.3
通讯作者：
Kaufman, Howard L.
中科院分区：
文献类型：
--
作者：
Sabatino, Marianna;Kim-Schulze, Seunghee;Kaufman, Howard L.
目的大剂量白介素2(IL-2)在一小部分转移性黑色素瘤和肾癌患者中诱导持久的治疗反应，但简单的治疗前预测反应的指标尚未确定。为了确定临床反应的预测生物标志物，我们收集了大剂量IL-2治疗患者的血清，使用定制的、多抗体靶向的蛋白质阵列平台进行分析，该平台调查了与肿瘤免疫生物学相关的可溶性因子的表达。结果来自10名患者的训练集确定了68个潜在相关的可溶因素，然后在49名患者的独立验证集中进行了测试。类别比较揭示了一组与治疗结果相关的11个生物标记物。血管内皮生长因子(VEGF)和纤维连接蛋白被确认为应答的独立预测因子。结论血清血管内皮生长因子和纤维连接蛋白是易于检测的治疗前生物标志物，可用于排除对IL-2治疗无效的患者。J Clin Oncol27：2645-2652。(C)2009年美国临床肿瘤学会
PurposeHigh-dose interleukin-2 (IL-2) induces durable therapeutic responses in a small subset of patients with metastatic melanoma and renal cell carcinoma, but simple pretreatment predictors of response have not been identified.Patients and MethodsTo identify predictive biomarkers of clinical response, sera from patients treated with high-dose IL-2 were collected for analysis using a customized, multiplex antibody-targeted protein array platform that surveyed expression of soluble factors associated with tumor immunobiology. Soluble factors associated with clinical responses were analyzed using a multivariate permutation test, and survival outcomes were determined using Kaplan-Meier and log-rank tests.ResultsA training set from 10 patients identified 68 potentially relevant soluble factors that were then tested in an independent validation set of 49 patients. Class comparison revealed a cluster of 11 biomarkers that were associated with therapeutic outcome. Vascular endothelial growth factor (VEGF) and fibronectin were identified as independent predictors of response. In particular, high levels of these proteins were correlated with lack of clinical response and decreased overall survival.ConclusionSerum VEGF and fibronectin are easily measured pretreatment biomarkers that could serve to exclude patients unlikely to respond to IL-2 therapy. J Clin Oncol 27:2645-2652. (C) 2009 by American Society of Clinical Oncology