Zhu Jiejie, Wu Yumei, Ge Xiaoyuan, Chen Xinwen, Mei Qiao
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People's Republic of China.
Key Laboratory of Digestive Diseases of Anhui Province, Hefei, People's Republic of China.
J Inflamm Res. 2024 Jul 9;17:4467-4482. doi: 10.2147/JIR.S463042. eCollection 2024.
Ulcerative colitis (UC) is a long-lasting idiopathic condition, but its precise mechanisms remain unclear. Meanwhile, evidence has demonstrated that ferroptosis seems to interlock with the progress of UC. This research sought to identify hub genes of UC related to ferroptosis.
First, the relevant profiles for this article were obtained from GEO database. From the FerrDb, 479 genes linked to ferroptosis were retrieved. Using analysis of the difference and WGCNA on colonic samples from GSE73661, the remaining six hub genes linked to ferroptosis and UC were discovered. Through logistic regression analyses, the diagnostic model was constructed and was then evaluated by external validation using dataset GSE92415. Afterwards, the correlation between immune cell filtration in UC and hub genes was examined. Finally, a mice model of colitis was established, and the results were verified using qRT-PCR.
We acquired six hub genes linked to ferroptosis and UC. In order to create a diagnostic model for UC, we used logistic regression analysis to screen three of the six ferroptosis related genes (HIF1A, SLC7A11, and LPIN1). The ROC curve showed that the three hub genes had outstanding potential for disease diagnosis (AUC = 0.976), which was subsequently validated in samples from GSE92415 (AUC = 0.962) and blood samples from GSE3365 (AUC = 0.847) and GSE94648 (AUC = 0.769). These genes might be crucial for UC immunity based upon the results on the immune system. Furthermore, mouse samples examined using qRT-PCR also verified our findings.
In conclusion, the findings have important implications for ferroptosis and UC, and these hub genes may also offer fresh perspectives on the aetiology and therapeutic approaches of UC.
溃疡性结肠炎（UC）是一种慢性特发性疾病，但其确切机制仍不清楚。同时，有证据表明铁死亡似乎与UC的进展相关。本研究旨在确定与铁死亡相关的UC核心基因。
首先，从GEO数据库获取本文相关的数据集。从FerrDb中检索到479个与铁死亡相关的基因。通过对GSE73661结肠样本进行差异分析和加权基因共表达网络分析（WGCNA），发现了另外六个与铁死亡和UC相关的核心基因。通过逻辑回归分析构建诊断模型，然后使用数据集GSE92415进行外部验证评估。之后，研究了UC中免疫细胞浸润与核心基因之间的相关性。最后，建立了结肠炎小鼠模型，并使用qRT-PCR验证结果。
我们获得了六个与铁死亡和UC相关的核心基因。为了创建UC的诊断模型，我们使用逻辑回归分析从六个与铁死亡相关的基因中筛选出三个（HIF1A、SLC7A11和LPIN1）。ROC曲线显示这三个核心基因具有出色的疾病诊断潜力（AUC = 0.976），随后在GSE92415样本（AUC = 0.962）以及GSE3365（AUC = 0.847）和GSE94648（AUC = 0.769）的血液样本中得到验证。基于免疫系统的结果，这些基因可能对UC免疫至关重要。此外，使用qRT-PCR检测的小鼠样本也验证了我们的发现。
总之，这些发现对铁死亡和UC具有重要意义，这些核心基因也可能为UC的病因学和治疗方法提供新的视角。
