Kamai Takao, Yanai Yoshiaki, Arai Kyoko, Abe Hideyuki, Yamanishi Tomonori, Kurimoto Masashi, Yoshida Ken-Ichiro
Department of Urology, Dokkyo Medical University, Tochigi, Japan.
BMC Cancer. 2007 Aug 15;7:159. doi: 10.1186/1471-2407-7-159.
Interferon-alpha (IFN-alpha) is one of the central agents in immunotherapy for renal cell carcinoma (RCC) and binds to the IFN-alpha receptor (IFNAR). We investigated the role of IFNAR in RCC.
We quantified IFNAR mRNA expression in paired tumor and non-tumor samples from the surgical specimens of 103 consecutive patients with RCC using a real-time reverse transcription polymerase chain reaction (RT-PCR), and IFNAR2 protein using Western blotting.
The absolute level of IFNAR1 and IFNAR2 mRNAs in tumor and non-tumor tissues did not correlate with the malignant and metastatic profiles. The relative yields of the PCR product from the tumor tissue to that from the corresponding non-tumor tissue (T/N) for the expression of IFNAR mRNAs were calculated. While the T/N ratio of IFNAR1 did not correlate with any factor, a high T/N ratio of IFNAR2 correlated with poor differentiation (P < 0.05), local invasion (P < 0.001), and metastasis (P < 0.0001). By multivariate analysis, a high T/N ratio of IFNAR2 predicted a shortened overall survival in all cases (P < 0.05) and a shorter disease-free survival in those without metastasis (M0; 68 cases, P < 0.05). Impressively, patients with a poorer response to IFN-alpha treatment had a higher IFNAR2 T/N ratio than those who had a good response (P < 0.05). IFNAR2c protein expression was higher in the primary tumors in patients with metastases (M1; 35 cases) compared to those without ( P < 0.0001).
IFNAR2 is associated with the progression of RCC.
α干扰素（IFN-α）是肾细胞癌（RCC）免疫治疗的核心药物之一，可与α干扰素受体（IFNAR）结合。我们研究了IFNAR在RCC中的作用。
我们使用实时逆转录聚合酶链反应（RT-PCR）对103例连续RCC患者手术标本中的配对肿瘤和非肿瘤样本中的IFNAR mRNA表达进行定量，并使用蛋白质印迹法对IFNAR2蛋白进行定量。
肿瘤组织和非肿瘤组织中IFNAR1和IFNAR2 mRNA的绝对水平与恶性和转移特征无关。计算肿瘤组织与相应非肿瘤组织PCR产物的相对产量（T/N）以评估IFNAR mRNA的表达。虽然IFNAR1的T/N比值与任何因素均无相关性，但IFNAR2的高T/N比值与低分化（P<0.05）、局部侵袭（P<0.001）和转移（P<0.0001）相关。多因素分析显示，IFNAR2的高T/N比值预测所有病例的总生存期缩短（P<0.05），在无转移患者（M0；68例）中无病生存期缩短（P<0.05）。令人印象深刻的是，对IFN-α治疗反应较差的患者的IFNAR2 T/N比值高于反应良好的患者（P<0.05）。与无转移患者相比，转移患者（M1；35例）原发肿瘤中IFNAR2c蛋白表达更高（P<0.0001）。
IFNAR2与RCC的进展相关。
