Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancunerheng Rd, Guangzhou, Guangdong 510655, People's Republic of China.
Mol Biol Rep. 2013 May;40(5):3457-64. doi: 10.1007/s11033-012-2338-9. Epub 2013 Mar 8.
High density DNA methylation microarrays were used to study the differences of gene methylation level in six pairs of colorectal cancer (CRC) and adjacent normal mucosa. We analyzed the profile of methylated genes by NimbleGen Microarray and the biologic functions by NIH-NAVID. In addition, preliminary validation studies were done in six pairs of samples by MSP (methylation-specific PCR). A total of 4,644 genes had a difference in methylation levels. Among them 2,296 were hypermethylated (log2ratio > 1), 2,348 genes were hypomethylated (log2ratio < -1), in which 293 hypermethylated and 313 hypomethylated genes were unmapped according to the NIH-NAVID. All these genes were randomly distributed on all the chromosomes. However, chromosome 1 contained the most of the hypermethylated genes (232 genes), followed by chromosome 19 (149 genes), chromosome 11 (144 genes), chromosome 2 (141 genes), chromosomes 3 (127 genes). Through the analysis of the statistics, There were 2 hypermethylated/3 hypomethylated genes involved in six pairs of samples simultaneously, followed by 10/14 in five samples, 34/37 in four samples, 101/113 in three samples, 341/377 in two samples, 1,808/1,804 in one sample. According to gene ontology analysis, some physiological processes play important roles in the cell division and the development of tumor, such as apoptosis, DNA repair, immune, cell cycle, cell cycle checkpoint, cell adhesion and invasion etc. Through Preliminary validation, there were two genes (St3gal6, Opcml) in thirty top-ranking genes shown hypermethylated in six pairs of CRC and adjacent normal mucosa.
High density DNA methylation microarrays is an effective method for screening aberrantly methylated genes in CRC. The methylated genes should be further studied for diagnostic or prognostic markers for CRC.
使用高密度 DNA 甲基化微阵列研究六对结直肠癌 (CRC) 和相邻正常黏膜之间基因甲基化水平的差异。我们通过 NimbleGen 微阵列分析甲基化基因的图谱，并通过 NIH-NAVID 分析生物学功能。此外，我们在六对样本中通过 MSP（甲基化特异性 PCR）进行了初步验证研究。共有 4644 个基因的甲基化水平存在差异。其中 2296 个基因呈高甲基化（log2ratio>1），2348 个基因呈低甲基化（log2ratio<-1），根据 NIH-NAVID，其中 293 个高甲基化和 313 个低甲基化基因未映射。所有这些基因都随机分布在所有染色体上。然而，1 号染色体包含最多的高甲基化基因（232 个），其次是 19 号染色体（149 个）、11 号染色体（144 个）、2 号染色体（141 个）、3 号染色体（127 个）。通过统计学分析，有 2 个高甲基化/3 个低甲基化基因同时涉及六对样本，其次是五对样本中的 10/14、四对样本中的 34/37、三对样本中的 101/113、两对样本中的 341/377、一对样本中的 1808/1804。根据基因本体论分析，一些生理过程在肿瘤的细胞分裂和发育中发挥重要作用，如细胞凋亡、DNA 修复、免疫、细胞周期、细胞周期检查点、细胞黏附和侵袭等。通过初步验证，在六对 CRC 和相邻正常黏膜中，有两个排名前 30 的基因（St3gal6、Opcml）显示高甲基化。
高密度 DNA 甲基化微阵列是筛选 CRC 中异常甲基化基因的有效方法。这些甲基化基因应进一步研究，作为 CRC 的诊断或预后标志物。
