Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, China.
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, The Third Xiangya Hospital of Central South University, Changsha, China.
J Cell Mol Med. 2024 Aug;28(16):e70013. doi: 10.1111/jcmm.70013.
Crohn's disease (CD) presents with diverse clinical phenotypes due to persistent inflammation of the gastrointestinal tract. Its global incidence is on the rise. Neutrophil extracellular traps (NETs) are networks released by neutrophils that capture microbicidal proteins and oxidases targeting pathogens. Research has shown that NETs are implicated in the pathogenesis of several immune-mediated diseases such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease. The goal of this study was to identify a panel of NET-related genes to construct a diagnostic and therapeutic model for CD. Through analysis of the GEO database, we identified 1950 differentially expressed genes (DEGs) associated with CD. Gene enrichment and immune cell infiltration analyses indicate that neutrophil infiltrates and chemokine-related pathways are predominantly involved in CD, with other immune cells such as CD4 and M1 macrophages also playing a role in disease progression. Utilizing weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks, we identified six hub genes (SPP1, SOCS3, TIMP1, IRF1, CXCL2 and CD274). To validate the accuracy of our model, we performed external validation with statistical differences(p < 0.05). Additionally, immunohistochemical experiments demonstrated higher protein expression of the hub genes in colonic tissues from CD patients compared to healthy subjects (p < 0.05). In summary, we identified six effective hub genes associated with NETs as potential diagnostic markers for CD. These markers not only offer targets for future research but also hold promise for the development of novel therapeutic interventions for CD.
克罗恩病(CD)由于胃肠道持续炎症而呈现出多种临床表型。其全球发病率呈上升趋势。中性粒细胞胞外诱捕网(NETs)是由中性粒细胞释放的网络,捕获针对病原体的杀菌蛋白和氧化酶。研究表明,NETs 与几种免疫介导的疾病的发病机制有关,如类风湿关节炎、系统性红斑狼疮和炎症性肠病。本研究的目的是鉴定一组与 CD 相关的 NET 相关基因,以构建 CD 的诊断和治疗模型。通过对 GEO 数据库的分析,我们确定了 1950 个与 CD 相关的差异表达基因(DEGs)。基因富集和免疫细胞浸润分析表明,中性粒细胞浸润和趋化因子相关途径主要参与 CD,其他免疫细胞如 CD4 和 M1 巨噬细胞也在疾病进展中发挥作用。利用加权基因共表达网络分析(WGCNA)和蛋白质-蛋白质相互作用(PPI)网络,我们鉴定了六个枢纽基因(SPP1、SOCS3、TIMP1、IRF1、CXCL2 和 CD274)。为了验证我们模型的准确性,我们进行了外部验证,结果具有统计学差异(p<0.05)。此外,免疫组织化学实验表明,与健康受试者相比,CD 患者结肠组织中枢纽基因的蛋白表达更高(p<0.05)。总之,我们鉴定了六个与 NETs 相关的有效枢纽基因,作为 CD 的潜在诊断标志物。这些标志物不仅为未来的研究提供了目标,也为 CD 的新型治疗干预措施的开发提供了希望。