Xu Rong, Du Wei, Yang Qinglong, Du Ashuai
Department of Pathology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan, China.
Department of General Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
J Cell Mol Med. 2024 Aug;28(15):e18501. doi: 10.1111/jcmm.18501.
Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition regarded as a major risk factor for colitis-associated cancer. However, the underlying mechanisms of IBD remain unclear. First, five GSE data sets available in GEO were used to perform 'batch correction' and Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). Candidate molecules were identified using CytoHubba, and their diagnostic effectiveness was predicted. The CIBERSORT algorithm evaluated the immune cell infiltration in the intestinal epithelial tissues of patients with IBD and controls. Immune cell infiltration in the IBD and control groups was determined using the least absolute shrinkage selection operator algorithm and Cox regression analysis. Finally, a total of 51 DEGs were screened, and nine hub genes were identified using CytoHubba and Cytoscape. GSE87466 and GSE193677 were used as extra data set to validate the expression of the nine hub genes. CD4-naïve T cells, gamma-delta T cells, M1 macrophages and resting dendritic cells (DCs) are the main immune cell infiltrates in patients with IBD. Signal transducer and activator of transcription 1, CCR5 and integrin subunit beta 2 (ITGB2) were significantly upregulated in the IBD mouse model, and suppression of ITGB2 expression alleviated IBD inflammation in mice. Additionally, the expression of ITGB2 was upregulated in IBD-associated colorectal cancer (CRC). The silence of ITGB2 suppressed cell proliferation and tumour growth in vitro and in vivo. ITGB2 resting DCs may provide a therapeutic strategy for IBD, and ITGB2 may be a potential diagnostic marker for IBD-associated CRC.
炎症性肠病（IBD）是一种慢性全身性炎症性疾病，被视为结肠炎相关癌症的主要危险因素。然而，IBD的潜在机制仍不清楚。首先，使用GEO中可用的五个GSE数据集进行“批次校正”和稳健秩聚合（RRA），以识别差异表达基因（DEG）。使用CytoHubba识别候选分子，并预测其诊断有效性。CIBERSORT算法评估了IBD患者和对照组肠道上皮组织中的免疫细胞浸润情况。使用最小绝对收缩选择算子算法和Cox回归分析确定IBD组和对照组中的免疫细胞浸润情况。最后，共筛选出51个DEG，并使用CytoHubba和Cytoscape识别出9个枢纽基因。使用GSE87466和GSE193677作为额外数据集来验证这9个枢纽基因的表达。CD4纯真T细胞、γδT细胞、M1巨噬细胞和静息树突状细胞（DC）是IBD患者中的主要免疫细胞浸润类型。信号转导和转录激活因子1、CCR5和整合素亚基β2（ITGB2）在IBD小鼠模型中显著上调，抑制ITGB2表达可减轻小鼠的IBD炎症。此外，ITGB2在IBD相关结直肠癌（CRC）中的表达上调。ITGB2沉默在体外和体内均抑制细胞增殖和肿瘤生长。ITGB2静息DC可能为IBD提供一种治疗策略，并且ITGB2可能是IBD相关CRC的潜在诊断标志物。
