Han Lichun, Lin Guangfu, Lv Xiaodan, Han Bing, Xu Xiaofang, Li Yu, Li Shiquan, Chen Deyi, Huang Zhixi, Gu Guangli, Lv Xiaoping
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Department of Clinical Experimental Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Int J Med Sci. 2025 Mar 3;22(7):1680-1697. doi: 10.7150/ijms.107018. eCollection 2025.
Inflammatory bowel disease (IBD) is a persistent, non-specific inflammation affecting the intestines. Psoriasis is a long-lasting inflammatory disorder of the skin. There is a comorbidity correlation between IBD and psoriasis, but the specific pathogenesis of the comorbidity is unclear. In this study, we analyzed datasets sourced from the Gene Expression Omnibus (GEO) database, and identified shared genes of IBD and psoriasis through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Then three machine learning algorithms were applied to identify shared diagnostic genes. Next, the validation of shared diagnostic genes was evaluated with ROC curves, with the AUC determined. Subsequently, single sample gene set enrichment analysis (ssGSEA) and immune infiltration analysis were conducted. Furthermore, we obtained potential drugs such as securinine in the Drug Signature Database (DsigDB) and 7 traditional Chinese medicines in the Coremine database, which might have therapeutic effects on the comorbidity of IBD and psoriasis. Finally, we confirmed the expression of the shared diagnostic gene in colitis and psoriasis mice tissues through RT-PCR, Western blot and immunohistochemistry (IHC) methods. The results showed that AQP9 had the highest diagnostic value for two diseases. AQP9 had AUC values of 93.681% for UC, 89.629% for CD,and 78.689% for psoriasis in the internal validation datasets. In the external validation datasets, AQP9 had AUC values of 90.394% for UC, 93.909% for CD,and 82.906% for psoriasis. Immune infiltration analysis and ssGSEA revealed that AQP9 might impact the disease process of IBD and psoriasis by participating in the NF-kappaB signaling pathway, and modulating immune cell differentiation. Furthermore, the expression levels of AQP9 were consistently validated, showing upregulation in IBD and downregulation in psoriasis, compared to the control group. This study revealed the shared diagnostic genes and potential mechanisms of the comorbidity of IBD and psoriasis, providing new directions for future research on exploring the comorbidity mechanisms and treatment targets.
炎症性肠病（IBD）是一种影响肠道的持续性非特异性炎症。银屑病是一种皮肤的慢性炎症性疾病。IBD与银屑病之间存在共病相关性，但其共病的具体发病机制尚不清楚。在本研究中，我们分析了来自基因表达综合数据库（GEO）的数据，并通过差异表达分析和加权基因共表达网络分析（WGCNA）确定了IBD和银屑病的共享基因。然后应用三种机器学习算法来识别共享诊断基因。接下来，用ROC曲线评估共享诊断基因的验证情况，并确定AUC。随后进行单样本基因集富集分析（ssGSEA）和免疫浸润分析。此外，我们在药物特征数据库（DsigDB）中获得了一叶萩碱等潜在药物，并在Coremine数据库中获得了7种中药，这些药物可能对IBD和银屑病的共病具有治疗作用。最后，我们通过RT-PCR、蛋白质免疫印迹和免疫组织化学（IHC）方法证实了共享诊断基因在结肠炎和银屑病小鼠组织中的表达。结果表明，水通道蛋白9（AQP9）对这两种疾病具有最高的诊断价值。在内部验证数据集中，AQP9对溃疡性结肠炎（UC）的AUC值为93.681%，对克罗恩病（CD）的AUC值为89.629%，对银屑病的AUC值为78.689%。在外部验证数据集中，AQP9对UC的AUC值为90.394%，对CD的AUC值为93.909%，对银屑病的AUC值为82.906%。免疫浸润分析和ssGSEA显示，AQP9可能通过参与核因子κB信号通路并调节免疫细胞分化来影响IBD和银屑病的疾病进程。此外，与对照组相比，AQP9的表达水平得到了一致验证，在IBD中上调，在银屑病中下调。本研究揭示了IBD和银屑病共病的共享诊断基因和潜在机制，为未来探索共病机制和治疗靶点的研究提供了新方向。
