Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

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.