High Expression of Toll-Like Receptor 4/Myeloid Differentiation Factor 88 Signals Correlates with Poor Prognosis in Colorectal Cancer
EL Wang, ZR Qian, M Nakasono, T Tanahashi, Y Bando, E Kudo, M Shimada, T Sano. Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan; Tsurugi Municipal Handa-Hospital, Tokushima, Japan; Tokushima University Hospital, Tokushima, Japan; Institute of Health Biosciences, Tokushima, Japan
Background: The toll-like receptor (TLR) 4 signaling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signaling in colon tumorigenesis, we examined the expression of TLR4 and myeloid Differentiation Factor 88 (MyD88) in colorectal cancer (CRC).
Design: 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 analyzed.
Results: Compared to 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]. 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). 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 expression 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.
Conclusions: This study showed that high expression of TLR4 and MyD88 are associated with liver metastasis and are independent predictors of poor prognosis in patients with CRC.
Tuesday, March 23, 2010 11:15 AM
Platform Session: Section E, Tuesday Morning