Yu Y I, Wang Wei, Song Lei, Hu Wentao, Dong Chi, Pei Hailong, Zhou Guangming, Yue Zhongjin
Department of Urological Surgery, Key Laboratory of Urinary Diseases of Gansu Province, Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu 730000, P.R. China ; Medical College, Northwest University for Nationalities, Lanzhou, Gansu 730030, P.R. China.
Oncol Lett. 2015 Jun;9(6):2485-2494. doi: 10.3892/ol.2015.3138. Epub 2015 Apr 23.
Renal cell carcinoma (RCC) is a common tissue tumor that occurs across all age groups and has become one of the types of cancer with the fastest increasing incidence. Due to the resistance of RCC chemo- and radiotherapy, surgery is the only currently effective treatment. Therefore, specific markers for the diagnosis and prognosis of RCC are expected to result in novel methods of treatment. Ecto-5'-nucleotidase, also termed cluster of differentiation (CD)73, is a protein that is activated in several types of aggressive cancer and may promote cancer progression. CD73 was examined in the present study to determine the association between the protein and RCC. The expression levels of CD73 in 159 RCC tissue sections and 30 paratumorous normal renal tissue samples obtained from 235 patients that underwent nephrectomy were examined by immunohistochemical staining. By contrast, the expression level of P-glycoprotein (P-gp), a potential prognostic factor in RCC, was also examined in 85 RCC and 13 normal tissue samples. Intense CD73 expression was identified in 75 out of 159 RCC cell membranes compared with normal renal tissues. In contrast, there was high P-gp expression in the blood vessels of 42 out of 85 RCC tissues and there was no significant difference between the P-gp expression identified in RCC cells (34 out of 85) and the cell membrane of normal renal cells (2 out of 13). The expression level of CD73 in RCC cells was significantly associated with tumor type, tumor node metastasis (TNM) stage, and tumor grade. However, the expression of P-gp in RCC cells was only associated with the TNM stage and tumor grade. Using a multivariable Cox regression analysis, it was found that the median survival rate of RCC patients with intense CD73 expression in RCC cells was 62.06±5.35 months, which was drastically shorter compared with rare CD73 expression (103.72±3.67 months). In conclusion, the expression level of CD73 is significantly associated with RCC tumor progression and may serve as a favorable marker for the diagnosis and prognosis of RCC, in addition to being a therapeutic target for the treatment of RCC.
肾细胞癌(RCC)是一种常见的组织肿瘤,可发生于所有年龄组,已成为发病率增长最快的癌症类型之一。由于RCC对化疗和放疗具有抗性,手术是目前唯一有效的治疗方法。因此,RCC诊断和预后的特异性标志物有望带来新的治疗方法。外切5'-核苷酸酶,也称为分化簇(CD)73,是一种在几种侵袭性癌症类型中被激活的蛋白质,可能促进癌症进展。在本研究中检测了CD73,以确定该蛋白与RCC之间的关联。通过免疫组织化学染色检查了从235例行肾切除术的患者中获得的159个RCC组织切片和30个癌旁正常肾组织样本中CD73的表达水平。相比之下,还在85个RCC和13个正常组织样本中检测了RCC中一种潜在预后因素P-糖蛋白(P-gp)的表达水平。与正常肾组织相比,在159个RCC细胞膜中的75个中鉴定出强烈的CD73表达。相比之下,85个RCC组织中的42个血管中存在高P-gp表达,并且在RCC细胞(85个中的34个)和正常肾细胞的细胞膜(13个中的2个)中鉴定出的P-gp表达之间没有显著差异。RCC细胞中CD73的表达水平与肿瘤类型、肿瘤淋巴结转移(TNM)分期和肿瘤分级显著相关。然而,RCC细胞中P-gp的表达仅与TNM分期和肿瘤分级相关。使用多变量Cox回归分析发现,RCC细胞中CD73表达强烈的RCC患者的中位生存率为62.06±5.35个月,与罕见的CD73表达(103.72±3.67个月)相比明显更短。总之,CD73的表达水平与RCC肿瘤进展显著相关,除了作为RCC治疗的治疗靶点外,还可作为RCC诊断和预后的良好标志物。