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在肾透明细胞癌中 HOXA5 和 MSH2 基因的表观遗传失活。

Epigenetic inactivation of HOXA5 and MSH2 gene in clear cell renal cell carcinoma.

机构信息

Department of Urology, School of Medicine, Kyung Hee University, Seoul, Korea.

出版信息

Pathol Int. 2010 Oct;60(10):661-6. doi: 10.1111/j.1440-1827.2010.02578.x.

Abstract

The high-throughput method using microarray is an easy and fast way to analyze the methylation status of hundreds of preselected genes and to screen them for signatures in methylation. The aim of our study is to detect hypermethylated genes and to analyze the association between methylation status and clinicopathological parameters of clear cell renal cell carcinoma. The genetic substrate included 62 cancer tissues and 62 matched adjacent normal kidney tissues. We adapted the GoldenGate genotyping assay to determine the methylation state of 1505 specific CpG sites in 807 genes. We identified two genes (HOXA5 and MSH2) with β-value differences of more than 0.3 between cancer and normal tissues. The high methylation group in HOXA5 had high Fuhrman's nuclear grade (P= 0.041). Other data in HOXA5 and MSH2 were not significant with methylation status (P > 0.05). Survival curve of the high methylation group in HOXA5 was slightly lower than that of the low methylation group. However, the statistical significances of overall survival in HOXA5 and MSH2 were low (P > 0.05). We report the hypermethylation of two genes in clear cell renal cell carcinoma. The data we obtained could provide the basis for a diagnostic test pathological assessment, or prognosis in clear cell renal cell carcinoma.

摘要

采用微阵列的高通量方法是分析数百个预选基因甲基化状态并筛选甲基化特征的简单快捷方法。本研究旨在检测高甲基化基因,并分析其甲基化状态与肾透明细胞癌临床病理参数之间的关联。遗传底物包括 62 例癌组织和 62 例配对的正常肾组织。我们采用 GoldenGate 基因分型检测法确定了 807 个基因中 1505 个特定 CpG 位点的甲基化状态。我们发现了两个基因(HOXA5 和 MSH2)在癌组织和正常组织之间β值差异大于 0.3。HOXA5 中高甲基化组的 Fuhrman 核分级较高(P=0.041)。HOXA5 和 MSH2 中的其他数据与甲基化状态无显著差异(P>0.05)。HOXA5 中高甲基化组的生存曲线略低于低甲基化组,但 HOXA5 和 MSH2 的总生存率的统计学意义较低(P>0.05)。我们报告了肾透明细胞癌中两个基因的高甲基化。我们获得的数据可为肾透明细胞癌的病理评估、诊断检测或预后提供依据。

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