Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array.
Identification of TNF-alpha and MMP-9 as potential baseline predictive serum markers of sunitinib activity in patients with renal cell carcinoma using a human cytokine array.
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DOI：
10.1038/sj.bjc.6605409
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发表时间：
2009-12-01
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
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有几种药物可用于治疗转移性肾细胞癌 (MRCC)，并且需要预测标记来为每位患者确定最合适的治疗方法。我们的目标是确定 MRCC 中舒尼替尼活性的潜在预测标志物。我们连续收集了 31 名接受舒尼替尼治疗的患者的血清样本。使用人类细胞因子阵列分析了六名具有显着反应或明显进展的极端表型的患者的血清，该阵列评估了治疗前后的 174 种细胞因子。比较两组之间细胞因子信号强度的变化，并通过 ELISA 对所有患者评估最相关的细胞因子。 174 种细胞因子中有 27 种在两组之间存在显着差异。通过 ELISA 对 21 名可评估患者中的 5 种（TNF-α、MMP-9、ICAM-1、BDNF 和 SDF-1）进行了评估。无反应者中 TNF-α 和 MMP-9 基线水平显着升高，并且分别与总生存期和进展时间缩短显着相关。作为舒尼替尼活性预测标志物的 TNF-α 和 MMP-9 的 ROC 曲线下面积分别为 0.83 和 0.77。 TNF-α 和 MMP-9 的基线水平值得进一步研究，作为 MRCC 舒尼替尼活性的预测标志物。选择具有极端表型的患者似乎是识别潜在反应预测因素的有效方法。
Several drugs are available to treat metastatic renal-cell carcinoma (MRCC), and predictive markers to identify the most adequate treatment for each patient are needed. Our objective was to identify potential predictive markers of sunitinib activity in MRCC. We collected sequential serum samples from 31 patients treated with sunitinib. Sera of six patients with extreme phenotypes of either marked responses or clear progressions were analysed with a Human Cytokine Array which evaluates 174 cytokines before and after treatment. Variations in cytokine signal intensity were compared between both groups and the most relevant cytokines were assessed by ELISA in all the patients. Twenty-seven of the 174 cytokines varied significantly between both groups. Five of them (TNF-α, MMP-9, ICAM-1, BDNF and SDF-1) were assessed by ELISA in 21 evaluable patients. TNF-α and MMP-9 baseline levels were significantly increased in non-responders and significantly associated with reduced overall survival and time-to-progression, respectively. The area under the ROC curves for TNF-α and MMP-9 as predictive markers of sunitinib activity were 0.83 and 0.77. Baseline levels of TNF-α and MMP-9 warrant further study as predictive markers of sunitinib activity in MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
45.3
作者：
Eggert, A;Grotzer, MA;Evans, AE
通讯作者：
Evans, AE
DOI：
10.1073/pnas.0708148104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Ebos, John M. L.;Lee, Christina R.;Kerbel, Robert S.
通讯作者：
Kerbel, Robert S.
影响因子：
168.9
作者：
Escudier, Bernard;Pluzanska, Anna;Moore, Nicola
通讯作者：
Moore, Nicola
影响因子：
11.5
作者：
Ramaswamy, Bhuvaneswari;Elias, Anthony D.;Shapiro, Charles L.
通讯作者：
Shapiro, Charles L.