Proteomic identification of interleukin-2 therapy response in metastatic renal cell cancer.
Proteomic identification of interleukin-2 therapy response in metastatic renal cell cancer.
复制标题
转移性肾细胞癌中白细胞介素 2 治疗反应的蛋白质组学鉴定。
DOI：
10.1016/j.juro.2007.09.016
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Libermann,TowiaA
中科院分区：
文献类型：
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作者：
Jones,Jon;Otu,HasanH;Grall,Franck;Spentzos,Dimitrios;Can,Handan;Aivado,Manuel;Belldegrun,ArieS;Pantuck,AllanJ;Libermann,TowiaA
目的利用表面增强激光解吸/电离飞行时间质谱仪检测转移性肾癌患者白细胞介素2治疗有效和无效的预测蛋白质谱。材料与方法将56例转移性透明细胞癌患者在白细胞介素2治疗前的肾癌根治性切除标本中提取的蛋白质提取液应用于不同层析性质的蛋白质芯片阵列，用表面增强激光解吸/电离飞行时间质谱仪进行分析。应用类别预测算法来识别具有与白细胞介素2反应状态相关的表达值的蛋白质峰的子集。结果从513个蛋白质峰中，我们发现了11个预测因子集，其预测白介素2应答状态的准确率为86%(Fisher‘s p<；0.004，置换p<；0.01)。结果在一个独立的数据集中得到验证，总体准确率为72%(p<；0.05，排列p<；0.01)。在多变量分析中，经淋巴状态校正后，蛋白质组图谱与白细胞介素2反应显著相关(p<；0.04)。结论我们确定并验证了一种蛋白质组模式，它是白细胞介素2反应的独立预测因子。预测白介素2反应概率的能力可以有针对性地选择最有可能对白介素2有反应的患者，同时避免对不太可能有反应的患者产生不必要的毒性。这种蛋白质组学预测指标有可能显著帮助临床医生对转移性肾癌患者进行适当的治疗决策。
PurposeTo detect a predictive protein profile that distinguishes interleukin-2 therapy responders and nonresponders among patients with metastatic renal cell carcinoma we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.Materials and MethodsProtein extracts from 56 patients with metastatic clear cell patients renal cell carcinoma obtained from radical nephrectomy specimens before interleukin-2 therapy were applied to protein chip arrays of different chromatographic properties and analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. A class prediction algorithm was applied to identify a subset of protein peaks with expression values associated with interleukin-2 response status. Multivariate analysis was performed to assess the association between the proteomic profile and interleukin-2 response status, controlling for the effect of lymphadenopathy.ResultsFrom 513 protein peaks we discovered a predictor set of 11 that performed optimally for predicting interleukin-2 response status with 86% accuracy (Fisher’s p <0.004, permutation p <0.01). Results were validated in an independent data set with 72% overall accuracy (p <0.05, permutation p <0.01). On multivariate analysis the proteomic profile was significantly associated with the interleukin-2 response when corrected for lymph node status (p <0.04).ConclusionsWe identified and validated a proteomic pattern that is an independent predictor of the interleukin-2 response. The ability to predict the probability of the interleukin-2 response could permit targeted selection of the patients most likely to respond to interleukin-2, while avoiding unwanted toxicity in patients less likely to respond. This proteomic predictor has the potential to significantly aid clinicians in the decision making of appropriate therapy for patients with metastatic renal cell carcinoma.