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血清中PCDH17(原钙黏蛋白17)启动子异常甲基化及其在肾细胞癌中的临床意义

Aberrant Promoter Methylation of PCDH17 (Protocadherin 17) in Serum and its Clinical Significance in Renal Cell Carcinoma.

作者信息

Lin Ying-Li, Wang Yun-Peng, Li Hong-Zhao, Zhang Xu

机构信息

Department of Urology, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, China (mainland).

Department of Urology, Xuzhou Cancer Hospital, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou, Jiangsu, China (mainland).

出版信息

Med Sci Monit. 2017 Jul 8;23:3318-3323. doi: 10.12659/msm.902077.

Abstract

BACKGROUND Current studies indicated that PCDH17 functions as a tumor suppressor, which is frequently inactivated by aberrant promoter methylation in urologic tumors. The main purpose of this study was to investigate the methylation status of PCDH17 in serum and its clinical significance in renal cell carcinoma (RCC). MATERIAL AND METHODS The methylation status of PCDH17 in serum samples of 142 RCC patients and 34 controls was evaluated by methylation-specific PCR (MSP). Then we correlated PCDH17 methylation status with the clinicopathologic features of RCC patients and patient outcomes. RESULTS We found that PCDH17 was more frequently methylated in RCC patients than in controls. Moreover, PCDH17 methylation in serum was significantly correlated with advanced stage (p=0.044), higher grade (p=0.019), lymph node metastasis (p=0.008) and tumor progression (p<0.001). In addition, patients with methylated PCDH17 had shorter progression-free survival (p<0.001) and overall survival (p=0.017) than patients without, and PCDH17 methylation in serum was an independent prognostic factor for worse progression-free survival (HR: 4.215, 95% CI: 1.376-9.032, p<0.001) and overall survival (HR: 5.092, 95% CI: 1.149-12.357, p=0.046) of patients with RCC. CONCLUSIONS The present study indicates that PCDH17 methylation in serum is a frequent event in RCC and associated with risk factors of poor outcomes. Moreover, PCDH17 methylation in serum is a potential prognostic biomarker for patients with RCC after surgery.

摘要

背景 目前的研究表明,PCDH17作为一种肿瘤抑制因子,在泌尿系统肿瘤中常因启动子异常甲基化而失活。本研究的主要目的是探讨PCDH17在血清中的甲基化状态及其在肾细胞癌(RCC)中的临床意义。材料与方法 采用甲基化特异性PCR(MSP)检测142例RCC患者和34例对照血清样本中PCDH17的甲基化状态。然后将PCDH17甲基化状态与RCC患者的临床病理特征及患者预后进行相关性分析。结果 我们发现RCC患者中PCDH17甲基化的频率高于对照组。此外,血清中PCDH17甲基化与晚期(p = 0.044)、高分级(p = 0.019)、淋巴结转移(p = 0.008)及肿瘤进展(p < 0.001)显著相关。另外,PCDH17甲基化的患者无进展生存期(p < 0.001)和总生存期(p = 0.017)均短于未甲基化的患者,血清中PCDH17甲基化是RCC患者无进展生存期(HR:4.215,95%CI:1.376 - 9.032,p < 0.001)和总生存期(HR:5.092,95%CI:1.149 - 12.357,p = 0.046)较差的独立预后因素。结论 本研究表明,血清中PCDH17甲基化在RCC中常见,且与不良预后的危险因素相关。此外,血清中PCDH17甲基化是RCC患者术后潜在的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f560/5513564/6419e4bacfc6/medscimonit-23-3318-g001.jpg

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