Shalaby Sally M, El-Shal Amal S, Abdelaziz Lobna A, Abd-Elbary Eman, Khairy Mostafa M
Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Gene. 2018 Feb 20;644:66-73. doi: 10.1016/j.gene.2017.10.056. Epub 2017 Nov 17.
Rectal cancer involves one-third of colorectal cancers (CRCs). Recently, data supported that DNA methylation have a role in CRC pathogenesis. In the present study we aimed to analyze the methylation status of MGMT and ERCC1 promoter regions in blood and tissue of patients with benign and malignant rectal tumors. We also studied the methylated MGMT and ERCC1 genes and their relations with clinicopathological features. Furthermore, we suggested that methylation may play a critical function in the regulation of MGMT and ERCC1 expression. Fifty patients with non-metastatic cancer rectum and 43 patients with benign rectal lesions were involved in the study. DNA extraction from blood and rectal specimens was done to analyze the methylation status of MGMT and ERCC1 genes by methylation-specific PCR method. RNA was extracted also to determine the expression levels of these genes by real time-PCR. The frequency of MGMT and ERCC1 methylation was significantly higher in rectum cancers than in benign tumors both for the tissue and the blood (p<0.001). There was no relation between MGMT or ERCC1 methylation and clinicopathological features; while they were correlated with the response to therapy. An interesting finding that the agreement of the methylation levels in the blood and rectal tissue was classified as good (κ=0.78) for MGMT gene and as very good (κ=0.85) for ERCC1. Lastly, the MGMT and ERCC1 genes methylation was associated with down-regulation of their mRNA expression when compared with the non-methylated status. Our findings provided evidence that both blood and tumor tissue MGMT and ERCC1 methylation were associated with cancer rectum. MGMT or ERCC1 methylation in blood could be suitable non-invasive biomarkers differentiating benign and malignant rectal tumors. Furthermore, the methylation of the MGMT and ERCC1 promoter regions was associated with down-regulation of their mRNA expression.
直肠癌占结直肠癌（CRC）的三分之一。最近，有数据表明DNA甲基化在CRC发病机制中起作用。在本研究中，我们旨在分析良性和恶性直肠肿瘤患者血液和组织中MGMT和ERCC1启动子区域的甲基化状态。我们还研究了甲基化的MGMT和ERCC1基因及其与临床病理特征的关系。此外，我们认为甲基化可能在MGMT和ERCC1表达的调节中起关键作用。本研究纳入了50例非转移性直肠癌患者和43例良性直肠病变患者。从血液和直肠标本中提取DNA，采用甲基化特异性PCR方法分析MGMT和ERCC1基因的甲基化状态。同时提取RNA，通过实时PCR测定这些基因的表达水平。无论是组织还是血液，直肠癌中MGMT和ERCC1甲基化的频率均显著高于良性肿瘤（p<0.001）。MGMT或ERCC1甲基化与临床病理特征无关；但它们与治疗反应相关。一个有趣的发现是，血液和直肠组织中甲基化水平的一致性，对于MGMT基因被分类为良好（κ=0.78），对于ERCC1基因被分类为非常好（κ=0.85）。最后，与未甲基化状态相比，MGMT和ERCC1基因甲基化与它们的mRNA表达下调相关。我们的研究结果表明，血液和肿瘤组织中的MGMT和ERCC1甲基化均与直肠癌相关。血液中的MGMT或ERCC1甲基化可能是区分良性和恶性直肠肿瘤的合适非侵入性生物标志物。此外，MGMT和ERCC1启动子区域的甲基化与它们的mRNA表达下调相关。
