STAT3 polymorphism predicts interferon-alfa response in patients with metastatic renal cell carcinoma
STAT3 polymorphism predicts interferon-alfa response in patients with metastatic renal cell carcinoma
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DOI：
10.1200/jco.2006.09.8897
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发表时间：
2007-07-01
影响因子：
45.3
通讯作者：
Ogawa, Osamu
中科院分区：
文献类型：
--
作者：
Ito, Noriyuki;Eto, Masatoshi;Ogawa, Osamu
目的探讨基因多态性对α-干扰素疗效的影响（IFN-α）用于转移性肾细胞癌（MRCC），并寻找一个可靠的分子标记，以选择那些MRCC患者谁将受益于IFN-α免疫治疗。患者和方法我们进行了关联研究，其中463个单核苷酸多态性（SNP），在33个候选基因的基因分型在75例日本患者谁收到IFN-α MRCC.ResultsAfter调整肺转移，逐步Logistic回归分析显示，信号转导和激活因子3（STAT 3）的SNPs是最显着相关的更好的反应IFN-α。连锁不平衡作图显示，STAT 3 5'区的SNP rs 4796793是IFN-α应答的最显著预测因子（比值比[OR] = 2.73; 95%CI，1.38至5.78）。与GG + GC基因型相比，rs 4796793处的CC基因型显示出最高OR（OR = 8.38，95%CI，1.63至42.96）。STAT 3在B淋巴细胞系中的基因型依赖性表达和增强的生长抑制作用的IFN-α的STAT 3抑制在RCC细胞系支持本协会study.ConclusionThe本研究的结果表明，STAT 3多态性是一个有用的诊断标志物，预测的反应IFN-α治疗MRCC患者。需要利用IFN-α的有效应答标记物来建立个体最佳治疗策略，即使当使用较新的药物疗法作为MRCC的一线治疗时。
PurposeTo clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-alpha) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-alpha immunotherapy.Patients and MethodsWe carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-alpha for MRCC.ResultsAfter adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-alpha. Linkage disequilibrium mapping revealed that the SNP in the 5' region of STAT3, rs4796793, was the most significant predictor of IFN-alpha response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN-alpha by STAT3 suppression in an RCC cell line supported the results of the present association study.ConclusionThe present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-alpha therapy in patients with MRCC. An efficient response marker for IFN-alpha needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.