Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
School of Medicine, Badr University in Cairo (BUC), Egypt.
Asian Pac J Cancer Prev. 2024 Feb 1;25(2):627-636. doi: 10.31557/APJCP.2024.25.2.627.
The pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC) is thought to be related to immune response against gut microbiota. TLR4, IgA, and EpCAM have a role in intestinal local immune response and their altered expression related to both IBD and CRC. Lipopolysaccharide (LPS) is the main activator of TLR4. The objective of this study is to evaluate the possible role of intestinal microbiota in the pathogenesis of IBD and CRC through expression of TLR4, IgA and EpCAM.
One hundred five cases were divided into (Group 1/ Control: 10 sections of normal colonic mucosa, Group 2/CRC: 51 cases, Group 3/IBD: 44 cases). Immunohistochemistry for TLR4, IgA, and EpCAM was done. LPS was assessed in all groups. TLR4 gene and protein expression were assessed in colorectal cancer cell line by RT-PCR and immunocytochemistry.
There was a significant correlation between TLR4 and tumor grade (P value 0.003 and 0.01 respectively). A significant correlation was found between IgA expression and T stage (P value 0.02) and between EpCAM expression and histologic type (P value 0.02). In comparison of CRC patients to controls; there was a statistically significant different expression of TLR4 positivity, IgA positivity and EpCAM (P value <0.001, 0.004, <0.001 respectively). Patients with CRC were compared to colitis patients and there was a statistically significant different expression of IgA positivity and EpCAM expression (P value <0.001). There was significant higher expression of TLR4 in CRC cell line than the fibroblast by both PCR and immunocytochemistry (P-value: 0.003 and 0.024 respectively). LPS level in CRC patients was significantly higher than the control and IBD groups (P values <0.001 and <0.001 respectively).
TLR4, IgA, EpCAM expression in both CRC and IBD might be related to the pathogenic role of microbiota and could represent potential prevention modalities and therapeutic targets.
炎症性肠病（IBD）和结直肠癌（CRC）的发病机制被认为与肠道微生物群的免疫反应有关。TLR4、IgA 和 EpCAM 在肠道局部免疫反应中起作用，它们的表达改变与 IBD 和 CRC 都有关。脂多糖（LPS）是 TLR4 的主要激活剂。本研究的目的是通过 TLR4、IgA 和 EpCAM 的表达来评估肠道微生物群在 IBD 和 CRC 发病机制中的可能作用。
将 105 例病例分为（第 1 组/对照组：10 例正常结肠黏膜，第 2 组/CRC：51 例，第 3 组/IBD：44 例）。进行 TLR4、IgA 和 EpCAM 的免疫组织化学检查。所有组均评估 LPS。通过 RT-PCR 和免疫细胞化学评估 TLR4 基因和蛋白在结直肠癌细胞系中的表达。
TLR4 与肿瘤分级呈显著相关（P 值分别为 0.003 和 0.01）。IgA 表达与 T 分期（P 值分别为 0.02 和 0.02）和 EpCAM 表达与组织学类型（P 值分别为 0.02）之间存在显著相关性。与对照组相比，CRC 患者 TLR4 阳性、IgA 阳性和 EpCAM 阳性的表达有统计学显著差异（P 值均<0.001、0.004、<0.001）。与结肠炎患者相比，CRC 患者的 IgA 阳性和 EpCAM 表达有统计学显著差异（P 值均<0.001）。PCR 和免疫细胞化学均显示，CRC 细胞系中 TLR4 的表达明显高于成纤维细胞（P 值分别为 0.003 和 0.024）。CRC 患者的 LPS 水平明显高于对照组和 IBD 组（P 值分别为<0.001 和<0.001）。
CRC 和 IBD 中 TLR4、IgA、EpCAM 的表达可能与微生物群的致病作用有关，可能代表潜在的预防方式和治疗靶点。
