Agricultural Institute of Slovenia, Hacquetova ulica 17, SI-1000 Ljubljana, Slovenia.
Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000 Ljubljana, Slovenia.
Int J Mol Sci. 2023 Aug 11;24(16):12692. doi: 10.3390/ijms241612692.
The cytosine-phosphate-guanine (CpG) island methylator phenotype (CIMP) represents one of the pathways involved in the development of colorectal cancer, characterized by genome-wide hypermethylation. To identify samples exhibiting hypermethylation, we used unsupervised hierarchical clustering on genome-wide methylation data. This clustering analysis revealed the presence of four distinct subtypes within the tumor samples, namely, CIMP-H, CIMP-L, cluster 3, and cluster 4. These subtypes demonstrated varying levels of methylation, categorized as high, intermediate, and very low. To gain further insights, we mapped significant probes from all clusters to Ensembl Regulatory build 89, with a specific focus on those located within promoter regions or bound regions. By intersecting the methylated promoter and bound regions across all methylation subtypes, we identified a total of 253 genes exhibiting aberrant methylation patterns in the promoter regions across all four subtypes of colorectal cancer. Among these genes, our comprehensive genome-wide analysis highlights bone morphogenic protein 4 () as the most prominent candidate. This significant finding was derived through the utilization of various bioinformatics tools, emphasizing the potential role of in colorectal cancer development and progression.
胞嘧啶-磷酸-鸟嘌呤（CpG）岛甲基化表型（CIMP）是结直肠癌发生发展的途径之一，其特征是全基因组超甲基化。为了鉴定表现出高甲基化的样本，我们使用无监督层次聚类对全基因组甲基化数据进行了分析。该聚类分析显示，肿瘤样本中存在四种不同的亚型，分别为 CIMP-H、CIMP-L、cluster 3 和 cluster 4。这些亚型表现出不同程度的甲基化，分为高、中、低三种。为了进一步深入研究，我们将所有聚类的显著探针映射到 Ensembl Regulatory build 89，特别关注位于启动子区域或结合区域的探针。通过在所有甲基化亚型中交叉比较甲基化启动子和结合区域，我们总共鉴定到了 253 个在结直肠癌的四个亚型中都表现出启动子区域异常甲基化模式的基因。在这些基因中，我们的全基因组综合分析突出了骨形态发生蛋白 4（）作为最主要的候选基因。这一重要发现是通过利用各种生物信息学工具得出的，强调了在结直肠癌的发生和发展过程中可能存在的作用。
