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P2X7受体可预测透明细胞肾细胞癌患者的术后癌症特异性生存率。

P2X7 receptor predicts postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma.

作者信息

Liu Zheng, Liu Yidong, Xu Le, An Huimin, Chang Yuan, Yang Yuanfeng, Zhang Weijuan, Xu Jiejie

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Cancer Sci. 2015 Sep;106(9):1224-31. doi: 10.1111/cas.12736. Epub 2015 Jul 29.

Abstract

The P2X7 receptor, an ATP-gated plasma membrane ion channel, is involved in inflammation, apoptosis and cell proliferation, and thereby plays a crucial role during oncogenic transformation in various malignancies. This study aims to evaluate the impact of P2X7 receptor expression on postoperative cancer-specific survival of patients with clear-cell renal cell carcinoma (ccRCC). A total of 273 patients with ccRCC undergoing nephrectomy at a single institution were retrospectively enrolled in this study, among which 86 patients died of this disease and six patients died of other causes. Clinicopathologic features and cancer-specific survival (CSS) were recorded. P2X7 expression was assessed by immunohistochemistry in clinical specimens. Kaplan-Meier method with log rank test was performed to compare survival curves. Cox regression models were used to evaluate the prognostic values of variables on CSS. Concordance index was calculated to assess prognostic accuracy of prognostic models. Median follow-up period was 90 months (range, 11-120 months). Intratumoral P2X7 expression was significantly lower than peritumoral tissues (P < 0.001). Moreover, high intratumoral P2X7 expression, which was significantly associated with shorten CSS (P < 0.001), high TNM stage (P = 0.038), Fuhrman grade (P = 0.035), SSIGN (stage, size, grade, and necrosis) score (P = 0.021) and University of California Integrated Staging System (UISS) score (P = 0.007), was indicated to be an independent prognostic factor for CSS (hazard ratio [HR], 1.693; P = 0.034). The prognostic accuracy of TNM stage, UISS and SSIGN scoring models was improved when intratumoral P2X7 expression was added. Intratumoral P2X7 expression is a potential independent adverse prognostic indicator for postoperative CSS of patients with ccRCC.

摘要

P2X7受体是一种ATP门控的质膜离子通道,参与炎症、细胞凋亡和细胞增殖,因此在各种恶性肿瘤的致癌转化过程中起着关键作用。本研究旨在评估P2X7受体表达对透明细胞肾细胞癌(ccRCC)患者术后癌症特异性生存的影响。本研究回顾性纳入了在单一机构接受肾切除术的273例ccRCC患者,其中86例死于该病,6例死于其他原因。记录临床病理特征和癌症特异性生存(CSS)情况。通过免疫组织化学法评估临床标本中的P2X7表达。采用Kaplan-Meier法和对数秩检验比较生存曲线。使用Cox回归模型评估各变量对CSS的预后价值。计算一致性指数以评估预后模型的预后准确性。中位随访期为90个月(范围11 - 120个月)。肿瘤内P2X7表达明显低于瘤周组织(P < 0.001)。此外,肿瘤内高P2X7表达与CSS缩短(P < 0.001)、高TNM分期(P = 0.038)、Fuhrman分级(P = 0.035)、SSIGN(分期、大小、分级和坏死)评分(P = 0.021)以及加利福尼亚大学综合分期系统(UISS)评分(P = 0.007)显著相关,提示其为CSS的独立预后因素(风险比[HR],1.693;P = 0.034)。当加入肿瘤内P2X7表达时,TNM分期、UISS和SSIGN评分模型的预后准确性得到提高。肿瘤内P2X7表达是ccRCC患者术后CSS的潜在独立不良预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1f1/4582993/f671f097dfc0/cas0106-1224-f1.jpg

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