Methylation of the Polycomb Group Target Genes Is a Possible Biomarker for Favorable Prognosis in Colorectal Cancer
Methylation of the Polycomb Group Target Genes Is a Possible Biomarker for Favorable Prognosis in Colorectal Cancer
复制标题
DOI：
10.1158/1055-9965.epi-12-0755
复制
发表时间：
2012-11-01
影响因子：
3.8
通讯作者：
Al-Qahtani, Mohammed H.
中科院分区：
文献类型：
--
作者：
Dallol, Ashraf;Al-Maghrabi, Jaudah;Al-Qahtani, Mohammed H.
背景：结直肠癌（CRC）是沙特阿拉伯王国第二大常见癌症，发病率不断上升。DNA甲基化是CRC中常见的事件，它被认为是CRC癌变过程中的一个重要现象，对CRC的分类和预后有重要意义。为了深入了解沙特阿拉伯患者CRC的分子机制，我们分析了关键基因的DNA甲基化频率，（MLH 1、MSH 2、RASSF 1A、SLIT 2、MGMT 1、SFRP 1、MYOD 1、APC、CDKN 2A以及5种CIMP标志物）。结果：在多梳组靶基因（PCGT）中检测到最常见的甲基化频率，包括SFRP 1（70%）、MYOD 1（60.8%）、CRP 1（61.7%）和SLIT 2（56.7%）。此外，MGMT甲基化检测频率较高（68.3%）。RASSF 1A、APC和CDKN 2A甲基化频率分别为42.5%、25%和32.8%。甲基化事件的K-均值聚类分析导致根据检测到的甲基化水平将CRC样品聚类为三组。（PCGT甲基化和CIMP阴性）甲基化特征对男性患者具有良好的预后，而具有第1组罕见甲基化特征的老年患者的临床结局可能较差。PCGT基因沿着RASSF 1A、APC和MGMT的甲基化可潜在地用作CRC肿瘤的分类和预后的新生物标志物，并且与肿瘤起源无关。癌症流行病学生物标志物Prev; 21（11）; 2069-75。（C）2012年AACR。
Background: 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.Methods: 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.Results: 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.Conclusion: Group II (PCGT methylation and CIMP-negative) methylation signature carried a favorable prognosis for male patients, whereas older patients with group 1 rare methylation signature have a potentially poorer clinical outcome.Impact: 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. Cancer Epidemiol Biomarkers Prev; 21(11); 2069-75. (C)2012 AACR.