Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer
Usefulness of plasma epigenetic changes of five major genes involved in the pathogenesis of colorectal cancer
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DOI：
10.1007/s00384-012-1566-8
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发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Lee, Soong
中科院分区：
文献类型：
--
作者：
Pack, Seung-Chul;Kim, Hye-Ran;Lee, Soong
本研究的目的是调查已知参与结直肠癌（CRC）发病机制及其临床病理意义的五个基因（母亲抗十倍体麻痹同源物4、脆性组氨酸三联体蛋白、死亡相关蛋白激酶1、腺瘤性结肠息肉病（APC）和E-钙粘蛋白）启动子区域的甲基化状态。研究对象为60名 CRC 患者、40 名腺瘤性结直肠息肉患者和 60 名健康对照者。我们进一步入组了总共 16 名患者（2 名克罗恩病患者、2 名溃疡性结肠炎患者、1 名锯齿状腺瘤患者和 11 名结直肠癌患者）。使用甲基化特异性聚合酶链反应单链构象多态性分析测定外周血浆中五个基因的甲基化状态。本研究显示，用于检测 CRC 的最敏感的表观遗传标记是 E-钙粘蛋白 (60%)，其次是 APC (57%)。与非 CRC 患者相比，E-钙粘蛋白和 APC 具有相似的特异性，并且在 CRC 患者中分别扩增 84% 和 86%。此外，APC 是 I 期 CRC 中唯一显着增加的标志物（OR = 6.67，95 % CI = 1.19-23.4，P = 0.045），也是 I 期 CRC 中最敏感（57 %）和特异度（89 %）的标志物。虽然我们没有检查配对的癌症组织和血浆，但在我们有限数量的结直肠癌患者中，存在相对较高的一致率（60-80％）。血浆中的五个基因（启动子甲基化）是结直肠癌患者中统计学上显着的危险因素。在这项研究中，E-cad 和 APC 基因可能是血浆中特别有用的表观遗传生物标志物，可用于检测 CRC。此外，APC 或许能够识别早期潜在的 CRC。
The purpose of present study was to investigate the methylation status of the promoter region in five genes (mothers against decapentaplegic homolog 4, fragile histidine triad protein, death-associated protein kinase 1, adenomatous polyposis coli (APC), and E-cadherin), which are known to be involved in the pathogenesis of colorectal cancer (CRC) and its clinicopathological significance.The study subjects were 60 CRC patients, 40 patients with adenomatous colorectal polyp and 60 healthy control individuals. We further enrolled a total of 16 patients (two patients with Crohn's disease, two patients with ulcerative colitis, one patient with serrated adenoma, and 11 patients with colorectal cancer). The methylation states of the five genes were determined in peripheral blood plasma using methylation-specific polymerase chain reaction single-strand conformation polymorphism analysis.This study showed the most sensitive epigenetic markers, E-cadherin (60 %), followed by APC (57 %), for detecting CRC. E-cadherin and APC had similar specificities and amplified 84 and 86 %, respectively, of CRC patients compared to non-CRC patients. Additionally, APC was the only marker to be significantly increased (OR = 6.67, 95 % CI = 1.19-23.4, P = 0.045) and the most sensitive (57 %) and specific (89 %) marker in stage I CRC. Though we have not examined the paired cancer tissues and plasma, there was relatively high concordant rate (60-80 %) in our limited number of colorectal cancer patients.Five genes, promoter methylation, in plasma were statistically significant risk factors in CRC patients. In this study, E-cad and APC genes may be particularly useful epigenetic biomarkers in plasma for the detection of CRC. Additionally, APC may able to identify early potential CRC.