Awakura Yasuo, Nakamura Eijiro, Takahashi Takeshi, Kotani Hirokazu, Mikami Yoshiki, Kadowaki Tadashi, Myoumoto Akira, Akiyama Hideo, Ito Noriyuki, Kamoto Toshiyuki, Manabe Toshiaki, Nobumasa Hitoshi, Tsujimoto Gozoh, Ogawa Osamu
Department of Urology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
J Cancer Res Clin Oncol. 2008 Dec;134(12):1363-9. doi: 10.1007/s00432-008-0412-4. Epub 2008 May 16.
Renal cell carcinoma (RCC) is characterized by a variable and unpredictable clinical course. Thus, accurate prediction of the prognosis is important in clinical settings. We conducted microarray-based study to identify a novel prognostic marker in conventional RCC.
The present study included the patients surgically treated at Kyoto University Hospital. Gene expression profiling of 39 samples was carried out to select candidate prognostic markers. Quantitative real-time PCR of 65 samples confirmed the microarray experiment results. Finally, we evaluated the significance of potential markers at their protein expression level by immunohistochemically analyzing 230 conventional RCC patients.
Using expression profiling analysis, we identified 14 candidate genes whose expression levels predicted unfavorable disease-specific survival. Next, we examined the expression levels of nine candidate genes by quantitative real-time PCR and selected CUB-domain containing protein 1 (CDCP1) for further immunohistochemical analysis. Positive staining for CDCP1 inversely correlated with disease-specific and recurrence-free survivals. In multivariate analysis including clinical/pathological factors, CDCP1 staining was a significant predictor of disease-specific and recurrence-free survivals.
We identified CDCP1 as a potential prognostic marker for conventional RCC. Further studies might be required to confirm the prognostic value of CDCP1 and to understand its function in RCC progression.
肾细胞癌(RCC)具有多变且不可预测的临床病程。因此,准确预测预后在临床环境中很重要。我们开展了基于微阵列的研究,以在传统RCC中鉴定一种新的预后标志物。
本研究纳入了在京都大学医院接受手术治疗的患者。对39个样本进行基因表达谱分析,以选择候选预后标志物。对65个样本进行定量实时PCR,证实了微阵列实验结果。最后,我们通过免疫组织化学分析230例传统RCC患者,评估了潜在标志物在其蛋白质表达水平的意义。
通过表达谱分析,我们鉴定出14个候选基因,其表达水平可预测不良的疾病特异性生存。接下来,我们通过定量实时PCR检测了9个候选基因的表达水平,并选择含CUB结构域蛋白1(CDCP1)进行进一步的免疫组织化学分析。CDCP1的阳性染色与疾病特异性生存和无复发生存呈负相关。在包括临床/病理因素的多变量分析中,CDCP1染色是疾病特异性生存和无复发生存的显著预测因子。
我们鉴定出CDCP1作为传统RCC的潜在预后标志物。可能需要进一步研究来证实CDCP1的预后价值,并了解其在RCC进展中的作用。