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