GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression

GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression
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DOI:
10.1111/j.1464-410x.2011.10862.x
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发表时间:
2012-07-01
期刊:
影响因子:
4.5
通讯作者:
Serth, Juergen
Serth, Juergen
中科院分区:
医学2区
文献类型:
--
作者:
Peters, Inga;Eggers, Hendrik;Serth, Juergen

文献摘要

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目的探讨肾细胞癌(RCC)中是否存在GATA 5 CpG岛(CGI)甲基化,并与临床、病理特征相关。患者和方法使用定量联合亚硫酸氢盐限制性分析(COBRA)对117个RCC样本和89对相邻正常组织中的甲基化进行定量通过对照RCC细胞系的焦磷酸测序分析预先评估COBRA(相关系数,R = 0.95)。使用配对t检验对匹配的肿瘤组织(TU)和邻近的正常组织(adN)样品进行统计分析,logistic回归用于独立样本组的比较,考克斯回归用于无进展生存期的分析。(20.4%)比adN(7.9%,肿瘤中GATA 5甲基化的增加与转移有关在透明细胞RCC(ccRCC)组中,CGI甲基化(P = 0.005)和无进展生存期(P = 0.005,HR = 4.59)在晚期ccRCC(pT >= 3和/或N1、M1或G2-3/G3)中检测到的CGI甲基化超过在局部肿瘤(pT >= 3和/或N1、M1或G2-3/G3)中检测到的CGI甲基化。
OBJECTIVETo investigate whether GATA5 CpG island (CGI) methylation occurs in renal cell carcinoma (RCC) and is associated with clinical, histopathological characteristics or progression-free survival of patients.PATIENTS AND METHODSMethylation was quantified in 117 RCC samples and 89 paired adjacent normal tissues using quantitative combined bisulphite restriction analysis (COBRA).COBRA was evaluated in advance by pyrosequencing analyses of control RCC cell lines (coefficient of correlation, R = 0.95).Statistical analyses were carried out using the paired t-test for matched tumour tissue (TU) and adjacent normal tissue (adN) samples, logistic regression for comparisons of independent sample groups and Cox regression for analysis of progression-free survival.RESULTSIn the present study, we found a significant higher mean relative methylation in TU (20.4%) than in adN (7.9%, P < 0.001) in paired samples of all RCCs.Increased GATA5 methylation in tumours was associated with metastasis (P = 0.005) and decreased progression-free survival (P = 0.005, HR = 4.59) in the clear-cell RCC (ccRCC) group.CGI methylation in advanced ccRCCs (pT >= 3 and/or N1, M1 or G2-3/G3) exceeds those detected in localized tumours (pT