Li Lin, An Guangqi, Li Fuzhen, Zhang Donghui, Zhu Xinyue, Liang Chunyu, Zhao Yu, Xie Kunpeng, Zhou Pengyi, Zhu Haiyan, Jin Xuemin, Du Liping
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, Henan, People's Republic of China.
J Inflamm Res. 2025 Feb 4;18:1657-1678. doi: 10.2147/JIR.S497201. eCollection 2025.
Associations between ulcerative colitis (UC) and ankylosing spondylitis (AS) have been reported in multiple studies, but the common etiologies of UC and AS remain unknown. Thus, in the current study, we aimed to investigate the shared genes and relevant mechanisms in UC and AS.
Using datasets for UC (GSE113079) and AS (GSE1797879), we initially identified differentially expressed genes (DEGs) through differential expression analysis. The DEGs from both datasets were intersected to identify common DEGs, relevant to both UC and AS, which were used in receiver operating characteristic (ROC) curve analysis to confirm key genes in the shared pathway. Gene set enrichment analysis (GSEA) was used to obtain information on key gene pathways and interactions with UC or AS-related diseases, followed by immune infiltration analysis. Finally, peripheral blood samples of AS and UC were used to verify the mRNA expression of the eight key genes using reverse transcription-polymerase chain reaction (RT-PCR).
Our results revealed that GMFG, GNG11, CLEC4D, CMTM2, VAMP5, S100A8, S100A12 and DGKQ are potential diagnostic biomarkers of AS and UC. Rimegepant, eptinezumab, methotrexate, atogepant, and ubrogepant were identified as potential drugs for S100A12 and S100A8 in patients with UC and AS. GSEA showed that these key genes were associated with antigen processing and presentation, natural killer cell mediated cytotoxicity and the T cell receptor signaling pathway in AS and UC, and were significantly associated with immune cells in various immune-related pathways. Subsequent functional experiments revealed significant increases in the mRNA expressions of S100A12 and VAMP5 in patients with AS and UC. Additionally, CLEC4D mRNA expression was notably higher in patients with UC than in healthy controls.
Key genes and shared pathways were identified in UC and AS, which may improve understanding of their relationship and guide diagnosis and treatment strategies.
多项研究报道了溃疡性结肠炎（UC）与强直性脊柱炎（AS）之间的关联，但UC和AS的共同病因仍不清楚。因此，在本研究中，我们旨在探究UC和AS中的共享基因及相关机制。
利用UC（GSE113079）和AS（GSE1797879）的数据集，我们首先通过差异表达分析确定差异表达基因（DEG）。将两个数据集的DEG进行交集分析，以识别与UC和AS均相关的共同DEG，这些基因用于受试者工作特征（ROC）曲线分析，以确认共享通路中的关键基因。基因集富集分析（GSEA）用于获取关键基因通路以及与UC或AS相关疾病相互作用的信息，随后进行免疫浸润分析。最后，使用逆转录-聚合酶链反应（RT-PCR）对AS和UC的外周血样本进行检测，以验证8个关键基因的mRNA表达。
我们的结果显示，GMFG、GNG11、CLEC4D、CMTM2、VAMP5、S100A8、S100A12和DGKQ是AS和UC的潜在诊断生物标志物。利美尼定、eptinezumab、甲氨蝶呤、阿托西班和ubrogepant被确定为UC和AS患者中S100A12和S100A8的潜在药物。GSEA显示，这些关键基因与AS和UC中的抗原加工和呈递、自然杀伤细胞介导的细胞毒性以及T细胞受体信号通路相关，并且在各种免疫相关通路中与免疫细胞显著相关。随后的功能实验显示，AS和UC患者中S100A12和VAMP5的mRNA表达显著增加。此外，UC患者中CLEC4D的mRNA表达明显高于健康对照。
在UC和AS中鉴定出关键基因和共享通路，这可能有助于加深对它们之间关系的理解，并指导诊断和治疗策略。
