Pilo Jesús, Rego-Calvo Alejandro, García-Flores Libia-Alejandra, Arranz-Salas Isabel, Alvarez-Mancha Ana Isabel, Izquierdo Andrea G, Crujeiras Ana B, Alcaide Julia, Ortega-Castan Maria, Boughanem Hatim, Macías-González Manuel
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010 Malaga, Spain.
Institute of Biomedical Research in Malaga (IBIMA)-Bionand Platform, University of Malaga, 29010 Malaga, Spain.
Int J Mol Sci. 2025 Jul 25;26(15):7197. doi: 10.3390/ijms26157197.
Aberrant DNA methylation has been shown to be a fingerprint characteristic in human colorectal tumors. In this study, we hypothesize that investigating global DNA methylation could offer potential candidates for clinical application in CRC. The epigenome-wide association analysis was conducted in both the tumor area (N = 27) and the adjacent tumor-free (NAT) area (N = 15). We found 78,935 differentially methylated CpG sites (DMCs) (FDR < 0.05), 42,888 hypomethylated and 36,047 hypermethylation showing overall hypomethylation. Gene ontology and KEGG analysis of differentially methylated genes showed significant enrichment in developmental genes, as well as in genes involved in metabolic processes and the cell cycle, such as the TFGβ and cAMP signaling pathways. Through filtered analysis, we identified as the most epigenetically dysregulated gene, hypomethylated and downregulated in CRC (both with < 0.001) and associated with poor overall survival. In the functional analysis, was epigenetically regulated in a dose-dependent manner, suggesting a potential role in CRC. The epigenetic dysregulation and functional role of in CRC could have clinical implications, serving as indicators of malignant potential, with adverse effects associated with disease origin and progression in CRC.
异常的DNA甲基化已被证明是人类结肠直肠肿瘤的一个特征性指纹。在本研究中，我们假设研究全基因组DNA甲基化可为结直肠癌的临床应用提供潜在候选物。在肿瘤区域（N = 27）和相邻的无肿瘤区域（NAT）（N = 15）均进行了全表观基因组关联分析。我们发现了78,935个差异甲基化的CpG位点（DMCs）（FDR < 0.05），其中42,888个是低甲基化的，36,047个是高甲基化的，总体呈现低甲基化状态。对差异甲基化基因的基因本体论和KEGG分析表明，发育基因以及参与代谢过程和细胞周期的基因，如TGFβ和cAMP信号通路，有显著富集。通过筛选分析，我们确定[具体基因名称未给出]是在结直肠癌中表观遗传失调最严重的基因，在结直肠癌中低甲基化且下调（两者均P < 0.001），并与总体生存率差相关。在功能分析中，[具体基因名称未给出]以剂量依赖的方式受到表观遗传调控，表明其在结直肠癌中具有潜在作用。[具体基因名称未给出]在结直肠癌中的表观遗传失调和功能作用可能具有临床意义，可作为恶性潜能的指标，与结直肠癌的疾病起源和进展相关的不良影响有关。
