Kinouchi Toshiro, Uemura Motohide, Wang Cong, Ishizuya Yu, Yamamoto Yoshiyuki, Hayashi Takuji, Matsuzaki Kyosuke, Nakata Wataru, Yoshida Takahiro, Jingushi Kentaro, Kawashima Atsunari, Ujike Takeshi, Nagahara Akira, Fujita Kazutoshi, Imamura Ryoichi, Ueda Yuko, Kitae Kaori, Tsujikawa Kazutake, Nonomura Norio
Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Therapeutic Urologic Oncology, Osaka University Graduate School of Medicine, Suita, Japan.
Cancer Sci. 2017 Dec;108(12):2495-2502. doi: 10.1111/cas.13414. Epub 2017 Oct 25.
There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly upregulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by receiver operating characteristic curve analysis (sensitivity, 70.0%; specificity, 64.0%; area under the curve = 0.722; multiple logistic regression analysis: odds ratio, 1.07; 95% confidence interval, 1.03-1.11; P = 0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in PBMCs than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in PBMCs from healthy volunteers was significantly elevated following coculture with RCC cells compared to those cocultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC.
目前尚无用于常规临床诊断肾细胞癌(RCC)的血液生物标志物。我们聚焦于从RCC患者获取的外周血细胞的基因表达谱,以发现RCC诊断的新型生物标志物。通过微阵列分析和定量验证,发现CXCL7在RCC患者外周血细胞中显著上调。重要的是,即使在早期(pT1a)RCC患者获取的外周血细胞中也证实了CXCL7的异常表达,并且通过受试者工作特征曲线分析,外周血细胞中CXCL7的表达水平是RCC诊断的潜在独立生物标志物(敏感性为70.0%;特异性为64.0%;曲线下面积 = 0.722;多元逻辑回归分析:比值比为1.07;95%置信区间为1.03 - 1.11;P = 0.0004)。此外,原发性肿瘤切除后,外周血细胞中CXCL7的表达显著降低。与健康对照和RCC患者的中性粒细胞相比,PBMC中CXCL7的表达更高。有趣的是,与作为对照的正常细胞共培养相比,健康志愿者的PBMC与RCC细胞共培养后,CXCL7的表达显著升高。这些结果表明,外周血细胞中CXCL7的异常表达是由RCC细胞诱导的,可能作为RCC诊断的新型生物标志物。