Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 14, 2012; 18(38): 5360-5368
Published online Oct 14, 2012. doi: 10.3748/wjg.v18.i38.5360
Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas
Kunihiro Hosono, Eiji Yamada, Hiroki Endo, Hirokazu Takahashi, Masahiko Inamori, Yoshitaka Hippo, Hitoshi Nakagama, Atsushi Nakajima
Kunihiro Hosono, Eiji Yamada, Hiroki Endo, Hirokazu Takahashi, Masahiko Inamori, Atsushi Nakajima, Division of Gastroenterology, Yokohama City University School of Medicine, Yokohama 2360004, Japan
Yoshitaka Hippo, Hitoshi Nakagama, Division of Cancer Development System, National Cancer Center Research Institute, Tokyo 1040045, Japan
Author contributions: Hosono K performed most of the research and wrote the paper; Yamada E, Endo H and Takahashi H performed the endoscopies; Inamori M analyzed the data; Hippo Y, Nakagama H and Nakajima A were major contributors in revising the manuscript critically for important intellectual content.
Supported by Grant-in-Aid for Research from the Third-Term Comprehensive Control Research for Cancer Center of the Ministry of Health, Labor and Welfare, Japan; Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan (KIBAN-B); and the “Collaborative Development of Innovative Seeds” Grant Program from the Japan Science and Technology Agency
Correspondence to: Dr. Atsushi Nakajima, Professor, Division of Gastroenterology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 2360004, Japan. nakajima-tky@umin.ac.jp
Telephone: +81-45-7872640 Fax: +81-45-7843546
Received: March 6, 2012
Revised: June 7, 2012
Accepted: June 15, 2012
Published online: October 14, 2012
Abstract

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas.

METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK).

RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue.

CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.

Keywords: Tumor necrosis factor-α; Tumor necrosis factor receptor 1; c-Jun N-terminal kinase; Colorectal adenoma; Biomarker