Cheon Jaehwan, Kim Sang Hyun, Park Jaehyung, Kim Tae Hoon
Department of Otorhinolaryngology-Head & Neck Surgery, Korea University College of Medicine, Anam-ro 145, Seongbuk-gu, Seoul 02841, Republic of Korea.
Department of Biomedical Science, Korea University College of Medicine, Anam-ro 145, Seongbuk-gu, Seoul 02841, Republic of Korea.
Int J Mol Sci. 2025 Jun 13;26(12):5693. doi: 10.3390/ijms26125693.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation and debilitating symptoms that considerably impair life quality. UC is particularly prevalent in younger populations, where early diagnosis remains challenging owing to nonspecific symptoms and the potential progression to colitis-associated cancer (CAC). The GSE177044 dataset, consisting of whole blood samples, was analyzed to identify differentially expressed genes, perform gene annotation, analyze key signaling pathways, and detect key hub genes in UC using protein-protein interaction networks. Multiple UC datasets composed of colonic samples were used for validation and examination of methylation and age-related gene expression patterns. Further analyses were performed to explore the association between these key hub genes and colon adenocarcinoma (COAD). We identified four key hub genes-lipocalin-2 (), matrix metalloproteinase-9 (), S100 calcium-binding protein A9 (), and olfactomedin-4 ()-significantly up-regulated in UC, with showing epigenetic regulation and age-dependent expression patterns. Additionally, S100A9 was strongly associated with poor prognosis in COAD, displaying hypo-methylation and elevated expression, especially in myeloid cell types, and links to altered immune and molecular subtypes. Our findings confirmed the hypo-methylation-driven up-regulation of , , and in UC, suggesting their potential as blood-based diagnostic biomarkers. Notably, S100A9 has emerged as a promising biomarker for the early diagnosis of ulcerative colitis, particularly in pediatric and adolescent patients with UC. Moreover, S100A9 holds potential as a precision target to prevent progression from UC to CAC.
溃疡性结肠炎（UC）是一种慢性炎症性肠病，其特征为黏膜炎症和使人衰弱的症状，这些症状会严重损害生活质量。UC在年轻人群中尤为普遍，由于症状不具特异性以及有进展为结肠炎相关癌症（CAC）的可能性，早期诊断仍然具有挑战性。对包含全血样本的GSE177044数据集进行了分析，以识别差异表达基因、进行基因注释、分析关键信号通路，并使用蛋白质-蛋白质相互作用网络检测UC中的关键枢纽基因。使用由结肠样本组成的多个UC数据集进行验证以及甲基化和年龄相关基因表达模式的检查。进行了进一步分析以探索这些关键枢纽基因与结肠腺癌（COAD）之间的关联。我们鉴定出四个关键枢纽基因——脂钙蛋白-2（）、基质金属蛋白酶-9（）、S100钙结合蛋白A9（）和嗅觉介质-4（）——在UC中显著上调，其中 表现出表观遗传调控和年龄依赖性表达模式。此外，S100A9与COAD的不良预后密切相关，表现为低甲基化和表达升高，尤其是在髓样细胞类型中，并且与免疫和分子亚型的改变有关。我们的研究结果证实了UC中 、 和 由低甲基化驱动的上调，表明它们作为基于血液的诊断生物标志物的潜力。值得注意的是，S100A9已成为溃疡性结肠炎早期诊断的一个有前景的生物标志物，特别是在儿科和青少年UC患者中。此外，S100A9作为预防UC进展为CAC的精准靶点具有潜力。
