Deng Beiying, Zhen Junhai, Xiang Zixuan, Li Xiangyun, Tan Cheng, Chen Ying, He Pengzhan, Ma Jingjing, Dong Weiguo
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, People's Republic of China.
J Inflamm Res. 2024 Sep 13;17:6345-6362. doi: 10.2147/JIR.S479011. eCollection 2024.
Ulcerative colitis (UC) is a debilitating intestinal disorder that imposes a significant burden on those affected. Fatty acid metabolism plays a pivotal role in regulating immune cell function and maintaining internal homeostasis. This study investigates the biological and clinical significance of fatty acid metabolism within the context of UC.
Gene expression profiles from patients with UC and healthy controls were retrieved, enabling the identification of differentially expressed genes (DEGs) specific to UC. These DEGs were then intersected with genes related to fatty acid metabolism, resulting in the identification of differentially expressed fatty acid metabolism-related genes (FAM-DEGs). Machine learning was employed to pinpoint key feature genes from the FAM-DEGs, which were subsequently used to construct a predictive UC model and to uncover molecular subtypes associated with fatty acid metabolism in UC. An animal model of UC was established using 3% dextran sulfate sodium (DSS) administration. Western blot analysis confirmed the expression levels of genes in intestinal tissues.
The machine learning analysis identified three pivotal genes-ACAT1, ACOX2, and HADHB-culminating in a highly predictive nomogram. Consensus cluster analysis further categorized 637 UC samples into two distinct subgroups. The molecular subtypes related to fatty acid metabolism in UC exhibited significant differences in gene expression, biological activities, and enrichment pathways. Immune infiltration analysis highlighted elevated expression of two genes (excluding HADHB) in subtype 1, which corresponded with a marked increase in immune cell infiltration within this subtype. Western blot analysis demonstrated that ACAT1, ACOX2, and HADHB expression levels in the DSS group were significantly reduced, paralleling those observed in the normal group.
This study highlights the critical role of specific fatty acid metabolism-related genes in UC, emphasizing their potential as targets for therapeutic intervention and shedding light on the underlying mechanisms of UC progression.
溃疡性结肠炎（UC）是一种使人衰弱的肠道疾病，给患者带来沉重负担。脂肪酸代谢在调节免疫细胞功能和维持体内稳态方面起着关键作用。本研究探讨了UC背景下脂肪酸代谢的生物学和临床意义。
检索UC患者和健康对照的基因表达谱，以鉴定UC特有的差异表达基因（DEG）。然后将这些DEG与脂肪酸代谢相关基因进行交叉分析，从而鉴定出差异表达的脂肪酸代谢相关基因（FAM-DEG）。采用机器学习从FAM-DEG中找出关键特征基因，随后用于构建UC预测模型，并揭示与UC脂肪酸代谢相关的分子亚型。通过给予3%葡聚糖硫酸钠（DSS）建立UC动物模型。蛋白质免疫印迹分析证实了肠道组织中基因的表达水平。
机器学习分析确定了三个关键基因——ACAT1、ACOX2和HADHB，最终形成了一个高度预测性的列线图。一致性聚类分析进一步将637个UC样本分为两个不同的亚组。UC中与脂肪酸代谢相关的分子亚型在基因表达、生物学活性和富集途径上表现出显著差异。免疫浸润分析显示，亚型1中两个基因（不包括HADHB）的表达升高，这与该亚型中免疫细胞浸润的显著增加相对应。蛋白质免疫印迹分析表明，DSS组中ACAT1、ACOX2和HADHB的表达水平显著降低，与正常组观察到的水平相似。
本研究强调了特定脂肪酸代谢相关基因在UC中的关键作用，强调了它们作为治疗干预靶点的潜力，并揭示了UC进展的潜在机制。
