Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: Correlations with pathology and outcome
Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: Correlations with pathology and outcome
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DOI：
10.1016/j.canlet.2007.03.006
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发表时间：
2007-09-08
期刊：
影响因子：
9.7
通讯作者：
Weikert, Steffen
中科院分区：
文献类型：
--
作者：
Kempkensteffen, Carsten;Hinz, Stefan;Weikert, Steffen
通过启动子甲基化下调推定的肿瘤抑制基因XIAP相关因子I（XAF 1）的转录已被证明与胃癌和膀胱癌的肿瘤进展相关。本研究采用实时定量RT-PCR和甲基化特异性定量PCR方法检测了91例肾细胞癌（RCC）患者手术治疗后肿瘤组织中XAF 1的mRNA表达水平和甲基化状态。表达数据与组织病理学变量和结果相关。XAF 1表达水平与用于结果预测的标准病理学参数无关，但来自粗略和探索性多变量校正分析的结果显示，低XAF 1水平显著增加肿瘤复发（RR 4.6; CI 95%：1.4-14.6）和肿瘤相关死亡（RR 3.6; CI 95%：1.4-9.7）的相对风险（RR）。低XAF 1表达与短期无复发（p = 0.009）和疾病特异性生存（p = 0.005）的相关性在局部晚期（pT 3）肿瘤患者中最为明显。很少检测到XAF 1启动子甲基化（10%），但如果存在，XAF 1 mRNA表达水平与甲基化的标准化指数呈负相关（p = 0.01）。我们的研究结果表明，低XAF 1 mRNA表达水平与肾细胞癌患者不利的临床过程。启动子甲基化可能是肾细胞癌中XAF 1基因转录下调的机制之一，但可能不是必需的机制。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Transcriptional downregulation of the putative tumor suppressor gene XIAP-associated Factor I (XAF1) by promoter methylation has been shown to relate to tumor progression of gastric and bladder cancer. This study determined the mRNA expression levels and the methylation status of XAF1 by real-time RT-PCR and quantitative methylation specific PCR in tumor tissue obtained from 91 renal cell carcinoma (RCC) patients (median follow-up 50.5 months) following surgical treatment. Expression data was correlated to histopathological variables and outcome. XAF1 expression levels were not related to standard pathological parameters for outcome prediction but results from crude and explorative multivariable-adjusted analyses revealed low XAF1 levels to significantly increase the relative risk (RR) for tumor recurrence (RR 4.6; CI 95% 1.4-14.6) and tumor-related death (RR 3.6; CI 95%: 1.4-9.7). The association of low XAF1 expression with an abbreviated recurrence-free (p = 0.009) and disease-specific survival (p = 0.005) was most pronounced in patients with locally advanced (pT3) tumors. XAF1 promoter methylation was rarely detected (10%) but, if present, XAF1 mRNA expression levels correlated inversely to the normalized index of methylation (p = 0.01). Our findings suggest that low XAF1 mRNA expression levels relate to an unfavorable clinical course in RCC patients. Promoter methylation may be one, but probably not the essential mechanism for transcriptional downregulation of the XAF1 gene in RCC. (c) 2007 Elsevier Ireland Ltd. All rights reserved.