Kaddoura Rachid, Ghelani Hardik, Alqutami Fatma, Altaher Hala, Hachim Mahmood, Jan Reem Kais
Department of Basic Science, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab Emirates.
Life (Basel). 2023 Mar 2;13(3):680. doi: 10.3390/life13030680.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response.
In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes' annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes.
174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group.
We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.
炎症性肠病（IBD）的特征是胃肠道的慢性炎症。在生物治疗中，英夫利昔单抗成为首个被批准用于治疗IBD的抗肿瘤坏死因子（TNF）药物。尽管取得了这一成功，但英夫利昔单抗价格昂贵，常常无效，且伴有不良事件。预测英夫利昔单抗耐药性将改善总体潜在治疗效果。因此，迫切需要扩大对遗传学在IBD中的作用及其与治疗反应关联的研究范围。
在当前研究中，利用来自基因表达综合数据库（GEO）的公开可用IBD患者转录组学数据集进行计算机模拟分析，以识别参与IBD发病机制且可能作为英夫利昔单抗反应潜在生物标志物的差异表达基因（DEG）子集。发现有五个数据集符合纳入标准。通过GEOR2工具使用limma R软件包识别数据集中的DEG。每个数据集中探针注释的基因与所有其他数据集的DGE进行交叉分析。使用Metascape对鉴定出的基因进行富集基因本体聚类，以探索基因之间可能的联系或相互作用。
通过分析两个数据集（GSE14580和GSE73661），发现IBD患者与健康对照之间有174个DEG，这表明它们可能在IBD发病机制中起作用。在这174个DEG中，所有五个数据集共有的基因有五个（SELE、TREM1、AQP9、FPR2和HCAR3）。此外，与无反应组相比，这五个基因在英夫利昔单抗反应组中被鉴定为下调。
我们假设这些基因表达的改变导致IBD患者对英夫利昔单抗的反应受损。因此，这些基因可作为早期检测IBD患者英夫利昔单抗反应受损的潜在生物标志物。
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