Center of Excellence in Genomic Medicine Research, King Fahad Medical Research Center, King Abdulaziz University, P.O. Box 80216, 21589 Jeddah, Kingdom of Saudi Arabia.
Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2069-75. doi: 10.1158/1055-9965.EPI-12-0755. Epub 2012 Sep 25.
Colorectal cancer (CRC) is the second most common cancer in the Kingdom of Saudi Arabia with ever increasing incidence rates. DNA methylation is a common event in CRC where it is now considered an important phenomenon in CRC carcinogenesis and useful for the classification and prognosis of CRC.
To gain insight into the molecular mechanisms underpinning CRC in Saudi Arabian patients, we profiled the DNA methylation frequency of key genes (MLH1, MSH2, RASSF1A, SLIT2, HIC1, MGMT, SFRP1, MYOD1, APC, CDKN2A, as well as five CIMP markers) in 120 sporadic CRC cases. CRC tumors originating from the rectum, left, and right colons are represented in this cohort of formalin-fixed paraffin-embedded tissues.
The most common methylation frequency was detected in the polycomb group target genes (PCGT) including SFRP1 (70%), MYOD1 (60.8%), HIC1 (61.7%), and SLIT2 (56.7%). In addition, MGMT methylation was detected at a high frequency (68.3%). RASSF1A, APC, and CDKN2A methylation frequencies were 42.5%, 25%, and 32.8%, respectively. K-means clustering analysis of the methylation events results in the clustering of the CRC samples into three groups depending on the level of methylation detected.
Group II (PCGT methylation and CIMP-negative) methylation signature carried a favorable prognosis for male patients, whereas older patients with group I rare methylation signature have a potentially poorer clinical outcome.
Methylation of the PCGT genes along with RASSF1A, APC, and MGMT can be potentially used as a new biomarker for the classification and prognosis of CRC tumors and independently of where the tumor has originated.
结直肠癌（CRC）是沙特阿拉伯第二大常见癌症，其发病率呈不断上升趋势。在 CRC 中，DNA 甲基化是一种常见事件，现在被认为是 CRC 癌变过程中的一个重要现象，并且对 CRC 的分类和预后具有重要意义。
为了深入了解沙特阿拉伯患者 CRC 的分子机制，我们对 120 例散发性 CRC 病例中关键基因（MLH1、MSH2、RASSF1A、SLIT2、HIC1、MGMT、SFRP1、MYOD1、APC、CDKN2A 以及五个 CIMP 标志物）的 DNA 甲基化频率进行了分析。本研究队列包括来自直肠、左、右结肠的福尔马林固定石蜡包埋组织。
最常见的甲基化频率出现在多梳组靶基因（PCGT）中，包括 SFRP1（70%）、MYOD1（60.8%）、HIC1（61.7%）和 SLIT2（56.7%）。此外，MGMT 甲基化也被检测到很高的频率（68.3%）。RASSF1A、APC 和 CDKN2A 的甲基化频率分别为 42.5%、25%和 32.8%。对甲基化事件的 K-均值聚类分析结果表明，CRC 样本根据检测到的甲基化水平聚类成三组。
PCGT 甲基化和 CIMP 阴性的 II 组甲基化特征对男性患者具有良好的预后，而 I 组罕见甲基化特征的老年患者可能具有较差的临床结局。
PCGT 基因的甲基化以及 RASSF1A、APC 和 MGMT 的甲基化可以作为 CRC 肿瘤分类和预后的新生物标志物，并且与肿瘤起源无关。
