Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients.
Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients.
复制标题
DOI：
10.1016/j.yexmp.2009.09.012
复制
发表时间：
2010-02
影响因子：
3.6
通讯作者：
Soliman AS
中科院分区：
文献类型：
--
作者：
Iyer P;Zekri AR;Hung CW;Schiefelbein E;Ismail K;Hablas A;Seifeldin IA;Soliman AS
肝细胞癌（HCC）是全球第五大常见癌症和第四大癌症死亡原因。在过去10年中，埃及的HCC发病率翻了一番，这可能是由于丙型肝炎病毒（HCV）和乙型肝炎病毒（HBV）的高流行率，尽管HBV的发病率在1992年引入疫苗后有所下降。DNA甲基化异常可能在肝癌发生中起重要作用。肝活检是目前甲基化研究的金标准；然而，成像技术往往足以诊断，使组织样本越来越少。利用血浆DNA进行分子流行病学DNA甲基化研究的效果尚不清楚。我们比较了肿瘤组织和血浆中抑癌基因APC、FHIT、p15、p16和E-cadherin的肿瘤甲基化谱，以检验来自同一肝癌患者的两种类型标本之间的一致性。从埃及Gharbiah的一项病例对照研究中招募了28名组织和血浆DNA匹配的HCC患者。APC基因（23/28,82.1%,p=0.001）、FHIT基因（24/28,85.7%,p= 0.0001）、p15基因（25/28,89.2%,p=0.045）、p16基因（19/28,67.9%,p=0.037）、E-cadherin基因（22/28,78.5%,p=0.0008）与组织与血浆基因的一致性均有统计学意义。平均特异性分别为90%、86%、96%、86%和100%。在本研究中检测的任何基因的甲基化与肝炎病毒感染之间没有显著的关联。血浆DNA可用于检测该人群肝癌患者的甲基化谱。未来对更大样本量的研究应该调查HBV、HCV和其他危险因素发生率较高的人群的甲基化谱。
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer mortality globally. HCC incidence has doubled in Egypt in the past 10 years, which could be attributed to the high prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV), although HBV rates have declined after the introduction of the vaccine in 1992. Aberrant DNA methylation may play an important role in hepatocarcinogenesis. Liver biopsy is the current gold standard for methylation studies; however, imaging techniques often suffice for diagnosis making tissue samples increasingly scarce. The efficacy of conducting DNA methylation studies in molecular epidemiology using plasma DNA is still unclear. We compared tumor methylation profile for the tumor suppressor genes APC, FHIT, p15, p16, and E-cadherin in tumor tissues and plasma to test the concordance between the two types of specimen from the same HCC patients. Twenty-eight HCC patients with matching tissue and plasma DNA were recruited from a case—control study in Gharbiah, Egypt. Concordance between the tissue and plasma was statistically significant in all five genes as follows: APC (23/28, 82.1%, p=0.001), FHIT (24/28, 85.7%, p=.0001), p15 (25/28, 89.2%, p=0.045), p16 (19/28, 67.9%, p=0.037), and E-cadherin (22/28, 78.5%, p=0.0008). The average specificity was 90%, 86%, 96%, 86%, and 100%, respectively. There was no significant association between methylation and hepatitis viral infection for any of the genes tested in this study. Plasma DNA can be reliable for testing methylation profile in liver cancer patients in this population. Future studies on a larger sample size should investigate methylation profile in populations with higher rates of HBV, HCV, and other risk factors.