Expression and significance of TLR4 and HIF-1α in pancreatic ductal adenocarcinoma

AIM: To investigate the expression of toll-like receptor (TLR) 4, nuclear factor-kappa B (NF-kappa B) p65 and hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) in pancreatic ductal adenocarcinoma and their clinical significance. METHODS: The mRNA of TLR4 and HIF-1 alpha were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues, and expression of TLR4, NF-kappa B p65 and HIF-1 alpha protein were detected by immunohistochemistry in 65 cases of pancreatic ductal adenocarcinoma tissues and 38 cases of corresponding adjacent tissues. The relationship between TLR4 or HIF-1 alpha and pathologic features, as well as the association between TLR4 and HIF-1 alpha, were also analyzed. Kaplan-Meier method was used to assess the impact of expression of TLR4 and HIF-1 alpha on survival of patients with pancreatic cancer. RESULTS: The relative quantification of TLR4 and HIF-1 alpha mRNA in tumor tissues was 0.81 +/- 0.10 and 0.87 +/- 0.11, respectively, significantly higher than that in adjacent tissues (0.81 +/- 0.10 vs 0.70 +/- 0.16, P = 0.002; 0.87 +/- 0.11 vs 0.68 +/- 0.13, P = 0.000). The protein expression of TLR4, NF-kappa B p65 and HIF-1 alpha in tumor tissues was 69.20%, 66.15% and 70.80%, respectively, being significantly higher than that in adjacent normal tissues (69.20% vs 39.50%, P = 0.003; 66.15% vs 31.58%, P = 0.001; 70.80% vs 36.80%, P = 0.001). There was no significant correlation between TLR4 or HIF-1 alpha expression and the age, gender, tumor location, the degree of tumor differentiation in the patients (P > 0.05). However, there was significant correlation between the expression of TLR4 or HIF-1 alpha and tumor size, lymph node metastasis, venous invasion and clinical staging (P < 0.05). The expression of TLR4 and HIF-1 alpha had a significant impact on survival of patients with pancreatic adenocarcinoma. CONCLUSION: TLR4, NE-kappa B p65 and HIF-1 alpha are overexpressed in pancreatic adenocarcinoma, TLR4 may be partly involved in up-regulating HIF-1 alpha, and both synergestically promote development of pancreatic adenocarcinoma. (C) 2010 Baishideng. All rights reserved.