Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Clinical Center of Hirschsprung Disease and Allied Disorders, Wuhan, China.
Front Immunol. 2022 Sep 28;13:961217. doi: 10.3389/fimmu.2022.961217. eCollection 2022.
Although increasing evidence has supported that Hirschsprung disease (HSCR) is the risk factor for children developing Crohn's disease (CD), the common mechanism of its co-occurrence remains unknown. The purpose of this study is to further explore the underlying mechanism and biomarkers for the co-occurrence of HSCR and CD.
The Gene Expression Omnibus (GEO) database was used to obtain gene expression profiles for CD (GSE95095) and HSCR (GSE98502). Following the identification of the shared differentially expressed genes (DEGs) of CD and HSCR, functional annotation, protein-protein interaction (PPI) network creation, and module assembly were performed to discover hub genes. RT-qPCR was performed to validate the expression of the hub genes in HSCR samples. The receiver operating characteristic (ROC) curve was utilized to assess the accuracy of the hub genes as biomarkers in predicting CD in both the training dataset and test dataset.
A total of 103 common DEGs (50 downregulated genes and 53 upregulated genes) were chosen for further investigation. The importance of chemokines and cytokines in these two disorders is highlighted by functional analysis. MCODE plug identified three important modules, which functionally enriched the immune system process. Finally, nine hub genes were identified using cytoHubba, including IL1B, IL10, CXCL10, ICAM1, EGR1, FCGR3A, S100A12, S100A9, and FPR1. The nine hub genes were mainly enriched in immune- and inflammation-related pathways. External data profiles and RT-qPCR confirmed the expression of the nine hub genes in HSCR and CD. ROC analysis revealed that the nine hub genes had a strong diagnostic value.
Our study reveals the common pathogenesis of HSCR and CD. These hub genes and diagnostic models may provide novel insight for the diagnosis and treatment of HSCR complicated with CD.
越来越多的证据表明先天性巨结肠（HSCR）是儿童克罗恩病（CD）的发病风险因素，但两者共同发病的常见机制尚不清楚。本研究旨在进一步探讨 HSCR 和 CD 共同发病的潜在机制和生物标志物。
使用基因表达综合数据库（GEO）获取 CD（GSE95095）和 HSCR（GSE98502）的基因表达谱。在确定 CD 和 HSCR 的共享差异表达基因（DEGs）后，进行功能注释、蛋白质-蛋白质相互作用（PPI）网络构建和模块组装，以发现枢纽基因。通过实时定量 PCR（RT-qPCR）验证 HSCR 样本中枢纽基因的表达。利用受试者工作特征（ROC）曲线评估枢纽基因作为预测训练数据集和测试数据集中 CD 的生物标志物的准确性。
共选择了 103 个共同的 DEGs（50 个下调基因和 53 个上调基因）进行进一步研究。功能分析突出了趋化因子和细胞因子在这两种疾病中的重要性。MCODE 插件鉴定了三个重要模块，这些模块在功能上丰富了免疫系统过程。最后，使用 cytoHubba 鉴定了 9 个枢纽基因，包括 IL1B、IL10、CXCL10、ICAM1、EGR1、FCGR3A、S100A12、S100A9 和 FPR1。这 9 个枢纽基因主要富集在免疫和炎症相关通路中。外部数据谱和 RT-qPCR 证实了这 9 个枢纽基因在 HSCR 和 CD 中的表达。ROC 分析显示，这 9 个枢纽基因具有很强的诊断价值。
本研究揭示了 HSCR 和 CD 的共同发病机制。这些枢纽基因和诊断模型可能为诊断和治疗伴有 CD 的 HSCR 提供新的思路。
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