Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma.
Serum interferon alpha receptor 2 mRNA may predict efficacy of interferon alpha with/without low-dose sorafenib for metastatic clear cell renal cell carcinoma.
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DOI：
10.1007/s00262-011-0989-3
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Yoshida K
中科院分区：
文献类型：
--
作者：
Furuya N;Kamai T;Shirataki H;Yanai Y;Fukuda T;Mizuno T;Nakamura F;Kambara T;Nakanishi K;Abe H;Yoshida K
干扰素（IFN）α是肾细胞癌（RCC）免疫治疗的中心药物之一。它通过与IFN-α受体（IFNAR）结合发挥作用。我们以前报道过，肿瘤中IFNAR 2 mRNA表达的增加与RCC的转移潜能和进展有关，也与转移性RCC对IFN-α治疗的不良反应有关。本研究探讨了肾癌患者血清IFNAR 2的影响。我们通过实时逆转录聚合酶链反应（RT-PCR）检测了66例连续RCC患者手术标本中血清IFNAR 2 mRNA水平，并定量了成对肿瘤和非肿瘤组织中IFNAR mRNA的表达。我们还测量了磷酸化Akt（Ser-473）和磷酸化S6核糖体蛋白（Ser-235/236）蛋白水平在配对的肿瘤和非肿瘤组织转移性RCC患者的蛋白质免疫印迹。血清IFNAR 2 mRNA水平与肿瘤组织水平无相关性。血清IFNAR 2 mRNA水平与肿瘤大小呈正相关（P < 0.05），而与肿瘤分级、pT分期、转移、微血管浸润及血清C反应蛋白水平无相关性。对IFN-α ±索拉非尼治疗反应良好的患者血清IFNAR 2 mRNA水平显著高于反应较差的患者（P < 0.0001）。肿瘤组织IFNAR 2 mRNA水平和磷酸化S6核糖体蛋白（Ser-235/236）水平与转移潜能相关IFN-α ±索拉非尼治疗原发性肿瘤时，IFNAR 2 mRNA水平和磷酸化Akt（Ser-473）蛋白水平均较低的患者，其疗效较好，（IFN-α ± Sor：CR-PR）（P分别< 0.01和P < 0.05）。Kaplan-Meier生存分析显示，血清IFNAR 2 mRNA水平越高，治疗后患者的总生存期越长（P < 0.05），而肿瘤组织中IFNAR 2 mRNA水平越高，患者的总生存期越短（P < 0.01）。我们的研究结果表明，高水平的血清IFNAR 2 mRNA可能是一个有用的标志物，预测转移性RCC的反应IFN-α ±索拉非尼治疗。
Interferon (IFN) alpha is one of the central agents in immunotherapy for renal cell carcinoma (RCC). It acts by binding to the IFN-alpha receptor (IFNAR). We previously reported that increased tumor expression of IFNAR2 mRNA was associated with the metastatic potential and progression of RCC, as well as with a poor response of metastatic RCC to IFN-alpha therapy. This study investigated the influence of serum IFNAR2 in RCC patients. We measured serum IFNAR2 mRNA levels and quantified IFNAR mRNA expression in paired tumor and non-tumor tissues from the surgical specimens of 66 consecutive RCC patients by the real-time reverse transcription polymerase chain reaction (RT-PCR). We also measured phosphorylated Akt (Ser-473) and phosphorylated-S6 ribosomal protein (Ser-235/236) proteins levels in paired tumor and non-tumor tissues of patients with metastatic RCC by Western blotting. The serum level of IFNAR2 mRNA was not associated with its tumor tissue level. Serum IFNAR2 mRNA was positively correlated with tumor size (P < 0.05), but not with tumor grade, pT stage, metastasis, microscopic vascular invasion, or serum C-reactive protein. Serum levels of IFNAR2 mRNA were significantly higher in patients with a good response to IFN-alpha ± sorafenib than in those with a poor response (P < 0.0001). Tumor tissue IFNAR2 mRNA levels and phosphorylated-S6 ribosomal protein (Ser-235/236) levels were associated with metastatic potential (P < 0.001 and P < 0.01, respectively), and patients with a low IFNAR2 mRNA level and low phosphorylated Akt (Ser-473) protein level in the primary tumor showed a good response to IFN-α ± sorafenib (IFN-α ± Sor: CR-PR) (P < 0.01 and P < 0.05, respectively). Kaplan–Meier survival analysis showed that a higher serum IFNAR2 mRNA level was associated with longer overall survival of treated patients (P < 0.05), while a higher tumor tissue IFNAR2 mRNA level was related to shorter overall survival (P < 0.01). Our findings suggest that a high serum level of IFNAR2 mRNA may be a useful marker for predicting the response of metastatic RCC to IFN-alpha ± sorafenib therapy.
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影响因子：
6.4
作者：
Abe, Hideyuki;Kamai, Takao;Yoshida, Ken-ichiro
通讯作者：
Yoshida, Ken-ichiro
影响因子：
6.2
作者：
Jonasch E;Corn P;Pagliaro LC;Warneke CL;Johnson MM;Tamboli P;Ng C;Aparicio A;Ashe RG;Wright JJ;Tannir NM
通讯作者：
Tannir NM
影响因子：
4.8
作者：
Arsham, AM;Howell, JJ;Simon, MC
通讯作者：
Simon, MC
DOI：
10.2174/187153006778250019
发表时间：
2006-09-01
影响因子：
1.9
作者：
Frumento, Guido;Piazza, Tiziana;Ferrini, Silvano
通讯作者：
Ferrini, Silvano
影响因子：
45.3
作者：
Gollob, Jared A.;Rathmell, W. Kimryn;Wright, John J.
通讯作者：
Wright, John J.