Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas.
OBJECTIVE
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.


CONCLUSIONS
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.
Division of Gastroenterology, Yokohama City University School of Medicine, Yokohama 2360004, Japan.
Kunihiro
K
Hosono
Eiji
E
Yamada
Hiroki
H
Endo
Hirokazu
H
Takahashi
Masahiko
M
Inamori
Yoshitaka
Y
Hippo
Hitoshi
H
Nakagama
Atsushi
A
Nakajima
D000236:Adenoma / Q000097:blood* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood* / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000378:metabolism
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha