Identification of novel aberrant methylation of BASP1 and SRD5A2 for early diagnosis of hepatocellular carcinoma by genome-wide search
Identification of novel aberrant methylation of BASP1 and SRD5A2 for early diagnosis of hepatocellular carcinoma by genome-wide search
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DOI：
10.3892/ijo_00000082
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发表时间：
2008-11-01
影响因子：
5.2
通讯作者：
Oka, Masaaki
中科院分区：
文献类型：
--
作者：
Moribe, Toyoki;Iizuka, Norio;Oka, Masaaki
利用12，600个基因的表达谱进行了全基因组研究，以鉴定可用于肝细胞癌（HCC）早期诊断的甲基化基因。在检测的12，600个基因中，通过我们的统计学和CpG作图测试，我们确定了23个基因在HCC组织中的表达水平显著低于非HCC肝组织。在这23个基因中，通过亚硫酸氢盐处理直接测序的甲基化分析确定了20个TNM I期和II期HCC样本中异常甲基化的4个基因。通过定量测序对20例HCC和来自独立HCC患者队列的相应非肿瘤肝组织的4个基因进行进一步甲基化分析，发现2个基因BASP 1和SRD 5A2仅在HCC组织中异常甲基化，但在任何相应的非肿瘤肝组织中均未异常甲基化。值得注意的是，在该队列中，我们发现，当甲基化率的截止值为30%时，在11例TNM I期和11期HCC、10例高分化HCC和4例小HCC的所有病例中，BASP 1或SRD 5A2均异常甲基化
A genome-wide study using expression profiles of 12,600 genes was conducted to identify methylated genes that could be used for early diagnosis of hepatocellular carcinoma (HCC). Of the 12,600 genes examined, we identified 23 genes with significantly lower expression levels in HCC tissues than in non-HCC liver tissues by our statistical and CpG mapping tests. Of these 23 genes, methylation analysis by direct sequencing with bisulfite treatment determined 4 genes that were aberrantly methylated in 20 HCC samples of TNM stages I and II. Further methylation analysis of the 4 genes by quantitative sequencing with 20 HCCs and the corresponding non-tumor liver tissues from an independent cohort of HCC patients revealed that 2 genes, BASP1 and SRD5A2, were aberrantly methylated in only HCC tissues, though not in any corresponding non-tumor liver tissues. Notably, in the cohort we found that BASP1 or SRD5A2 were aberrantly methylated when a cut-off value of 30% in the methylation rate was used, in all cases of 11 HCCs of TNM stages I and 11, of 10 well-differentiated HCCs and of 4 small HCCs