Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis.
Differential methylation of the promoter and first exon of the RASSF1A gene in hepatocarcinogenesis.
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RASSF1A基因的启动子和第一个外显子在肝癌发生中的差异甲基化。
DOI：
10.1111/hepr.12449
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Su YH
中科院分区：
文献类型：
--
作者：
Jain S;Xie L;Boldbaatar B;Lin SY;Hamilton JP;Meltzer SJ;Chen SH;Hu CT;Block TM;Song W;Su YH
肿瘤抑制基因RASSF1A的启动子P2和第一外显子E1区域的异常甲基化与肝细胞癌（HCC）有关，尽管特异性较差。本研究分析了该基因P1， P2和E1区域的甲基化谱，以确定甲基化最特异性地对应HCC的区域，并评估该甲基化区域作为尿液中HCC筛查的生物标志物的潜力。通过亚硫酸氢盐DNA测序和定量甲基化特异性聚合酶链反应分析，比较从正常、肝炎、肝硬化、邻近非HCC和HCC肝组织和尿液样本中分离的DNA中P1、P2和E1区56个CpG位点的甲基化，以表征RASSF1A基因的高甲基化，作为HCC筛查的生物标志物。在组织中，将HCC （n = 120）与肝硬化和肝炎（n = 70）进行比较，P1甲基化的受试者工作特征曲线下面积（AUROC）为0.90，而E1和P2甲基化的AUROC分别为0.84和0.72。在90%的敏感性下，P1甲基化的特异性为72.9%，E1为38.6%，P2为27.1%。尿液中检测到与肝硬化和HCC相关的甲基化P1 DNA。对α-胎蛋白阴性HCC的敏感性为81.8%。在分析的三个区域中，P1的甲基化是HCC最特异性的，并且作为尿液中筛查肝硬化和HCC的DNA标记物具有很大的前景。
Aberrant methylation of the promoter, P2, and the first exon, E1, regions of the tumor suppressor gene RASSF1A, have been associated with hepatocellular carcinoma (HCC), albeit with poor specificity. This study analyzed the methylation profiles of P1, P2 and E1 regions of the gene to identify the region of which methylation most specifically corresponds to HCC and to evaluate the potential of this methylated region as a biomarker in urine for HCC screening. Bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays were performed to compare methylation of the 56 CpG sites in regions P1, P2 and E1 in DNA isolated from normal, hepatitic, cirrhotic, adjacent non-HCC, and HCC liver tissue and urine samples for the characterization of hypermethylation of the RASSF1A gene as a biomarker for HCC screening. In tissue, comparing HCC (n = 120) with cirrhosis and hepatitis together (n = 70), methylation of P1 had an area under the receiver operating characteristics curve (AUROC) of 0.90, whereas methylation of E1 and P2 had AUROC of 0.84 and 0.72, respectively. At 90% sensitivity, specificity for P1 methylation was 72.9% versus 38.6% for E1 and 27.1% for P2. Methylated P1 DNA was detected in urine in association with cirrhosis and HCC. It had a sensitivity of 81.8% for α-fetoprotein negative HCC. Among the three regions analyzed, methylation of P1 is the most specific for HCC and holds great promise as a DNA marker in urine for screening of cirrhosis and HCC.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
6
作者：
Lee, S;Lee, HJ;Kang, GH
通讯作者：
Kang, GH
影响因子：
4.7
作者：
Gao, Wentao;Kondo, Yutaka;Sekido, Yoshitaka
通讯作者：
Sekido, Yoshitaka
影响因子：
11.5
作者：
Chan, K. C. Allen;Leung, Sing F.;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis