Department of Human Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima, Japan.
Br J Cancer. 2010 Mar 2;102(5):908-15. doi: 10.1038/sj.bjc.6605558. Epub 2010 Feb 9.
The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC).
The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed.
Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS.
Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.
Toll 样受体（TLR）4 信号通路已被证明在体外和体内具有致癌作用。为了证明 TLR4 信号在结肠肿瘤发生中的作用，我们检查了结直肠癌（CRC）中 TLR4 和髓样分化因子 88（MyD88）的表达。
通过免疫组织化学检测 108 例 CRC 样本、15 例腺瘤和 15 例正常黏膜中 TLR4 和 MyD88 的表达，并分析其免疫评分与包括无病生存（DFS）和总生存（OS）在内的临床病理变量之间的相关性。
与正常黏膜和腺瘤相比，20%的癌症显示 TLR4 高表达，23%的癌症显示 MyD88 高表达。TLR4 和 MyD88 的高表达与肝转移显著相关（P=0.0001，P=0.0054）。在单因素分析中，TLR4 高表达与较短的 OS 显著相关（HR：2.17；95%CI：1.15-4.07；P=0.015）。MyD88 表达高与较差的 DFS 和 OS 显著相关（HR：2.33；95%CI：1.31-4.13；P=0.0038 和 HR：3.03；95%CI：1.67-5.48；P=0.0002）。TLR4 和 MyD88 的高联合表达也与较差的 DFS 和 OS 显著相关（HR：2.25；95%CI：1.27-3.99；P=0.0053 和 HR：2.97；95%CI：1.64-5.38；P=0.0003）。多因素分析显示，TLR4 高表达（OS：调整后的 HR：1.88；95%CI：0.99-3.55；P=0.0298）和 MyD88 高表达（DFS：调整后的 HR：1.93；95%CI：1.01-3.67；P=0.0441；OS：调整后的 HR：2.25；95%CI：1.17-4.33；P=0.0112）是 OS 的独立预后因素。此外，TLR4/MyD88 的高共表达与较差的 DFS 和 OS 密切相关。
我们的研究结果表明，TLR4 和 MyD88 的高表达与肝转移相关，是 CRC 患者预后不良的独立预测因子。
