Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jun 21, 2010; 16(23): 2881-2888
Published online Jun 21, 2010. doi: 10.3748/wjg.v16.i23.2881
Expression and significance of TLR4 and HIF-1α in pancreatic ductal adenocarcinoma
Jian-Jun Zhang, He-Shui Wu, Lin Wang, Yuan Tian, Jing-Hui Zhang, Hai-Long Wu
Jian-Jun Zhang, He-Shui Wu, Hai-Long Wu, Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Lin Wang, Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Yuan Tian, Jing-Hui Zhang, Laboratory of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Wu HS and Wang L designed the research; Zhang JJ, Tian Y, Zhang JH and Wu HL performed the research; Zhang JJ analyzed the data; Zhang JJ and Wu HS wrote the paper.
Supported by Grants from the National Natural Science Foundation of China, No. 30972898
Correspondence to: He-Shui Wu, MD, Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. heshuiwu@163.com
Telephone: +86-27-85351621 Fax: +86-27-85351673
Received: February 21, 2010
Revised: April 6, 2010
Accepted: April 13, 2010
Published online: June 21, 2010
Abstract

AIM: To investigate the expression of toll-like receptor (TLR) 4, nuclear factor-κB (NF-κB) p65 and hypoxia-inducible transcription factor 1α (HIF-1α) in pancreatic ductal adenocarcinoma and their clinical significance.

METHODS: The mRNA of TLR4 and HIF-1α were investigated by real-time polymerase chain reaction in 30 cases of pancreatic ductal adenocarcinoma and its adjacent tissues, and expression of TLR4, NF-κB p65 and HIF-1α 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-1α and pathologic features, as well as the association between TLR4 and HIF-1α, were also analyzed. Kaplan-Meier method was used to assess the impact of expression of TLR4 and HIF-1α on survival of patients with pancreatic cancer.

RESULTS: The relative quantification of TLR4 and HIF-1α 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-κB p65 and HIF-1α 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-1α 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-1α and tumor size, lymph node metastasis, venous invasion and clinical staging (P < 0.05). The expression of TLR4 and HIF-1α had a significant impact on survival of patients with pancreatic adenocarcinoma.

CONCLUSION: TLR4, NF-κB p65 and HIF-1α are overexpressed in pancreatic adenocarcinoma, TLR4 may be partly involved in up-regulating HIF-1α, and both synergestically promote development of pancreatic adenocarcinoma.

Keywords: Pancreatic ductal adenocarcinoma; Toll-like receptor 4; Nuclear factor-κB p65; Hypoxia-inducible factor 1