The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma
The assessment of methylated BASP1 and SRD5A2 levels in the detection of early hepatocellular carcinoma
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DOI：
10.3892/ijo_00000491
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发表时间：
2010-01-01
影响因子：
5.2
通讯作者：
Oka, Masaaki
中科院分区：
文献类型：
--
作者：
Tsunedomi, Ryouichi;Ogawa, Yasushi;Oka, Masaaki
我们先前从10，000多个筛选的基因中鉴定出BASP 1和SRD 5A2作为新的肝细胞癌（HCC）甲基化标志物。本研究旨在提高这些基因的诊断潜力。我们使用定量甲基化特异性PCR比较了46组HCC和相应的非肿瘤肝组织中BASP 1和SRD 5A2基因不同区域的甲基化状态。我们还研究了它们的表观遗传状态如何影响组织和几种肝癌细胞系中的转录水平。我们发现BASP 1和SRD 5A2基因座在超过50%的HCC组织中甲基化。在组织中的甲基化状态和转录水平之间确定了负相关。评估BASP 1和SRD 5A2的CpG岛甲基化率导致即使在相同的CpG岛中区分HCC的诊断能力也不同。BASP 1和SRD 5A2的组合分析产生了最佳诊断性能（84.8%的灵敏度和91.3%的特异性），受试者工作特征曲线下的最大面积为0.878。即使在早期HCC患者（分化良好，TNM I期和小直径）和血清甲胎蛋白阴性的患者中，联合分析也能准确诊断HCC。体外分析还表明，BASP 1和SRD 5A2转录本的表观遗传调控甲基化和乙酰化。这些结果表明，甲基化BASP 1和SRD 5A2的联合分析可能有助于准确诊断肝癌，尤其是早期肝癌。
We previously identified BASP1 and SRD5A2 as novel hepatocellular carcinoma (HCC) methylation markers from among more than 10,000 screened genes. The present study aimed to improve the diagnostic potential of these genes. We compared the methylation status at distinct regions of the BASP1 and SRD5A2 genes using quantitative methylation-specific PCR, in 46 sets of HCC and corresponding non-tumor liver tissues. We also examined how their epigenetic status affected transcript levels in tissues and several hepatoma cell lines. We found that BASP1 and SRD5A2 loci were methylated in greater than 50% of the HCC tissues. Inverse correlations were identified between the methylation status and transcript levels in the tissues. Assessment of CpG island methylation rate of BASP1 and SRD5A2 resulted in different diagnostic powers for discriminating HCC even in the same CpG island. A combination analysis of BASP1 and SRD5A2 resulted in the optimum diagnostic performance (84.8% sensitivity and 91.3% specificity) with a maximal area under the receiver operating characteristic curve of 0.878. Even in patients with early HCC (well-differentiated, TNM stage I and small in diameter) and those negative for serum alpha-fetoprotein, combination analysis enabled an accurate diagnosis of HCC. In vitro analysis also showed that BASP1 and SRD5A2 transcripts were epigenetically regulated by methylation and acetylation. These results suggest that combined analysis of methylated BASP1 and SRD5A2 may prove useful in the accurate diagnosis of HCC, especially early HCC.