Association between prognostic survival of human colorectal carcinoma and ZNRF3 expression

PURPOSE: E3 ubiquitin ligase ZNRF3 is linked to the pathogenesis of diseases and tumorigenesis. The present study aims to explore the expression of ZNRF3 and its association with prognostic survival of human colorectal carcinoma. METHODS: A follow-up survey of 168 patients with colorectal carcinoma was performed, and specimens of colorectal tissues were collected for immunohistochemistry and Western blotting analyses. Furthermore, overexpression of ZNRF3 using transient transfection with the recombinant pEGFP-ZNRF3 plasmid and detection of apoptosis and proliferation were performed in HCT-116 cells. RESULTS: The results showed a diverse feature of ZNRF3 staining, such as strong, moderate, weak, or negative, in colorectal carcinoma tissues. Interestingly, univariate Kaplan–Meier analysis showed that cases with strong or moderate expression of ZNRF3 showed an optimistic disease-free survival and overall survival compared with negative expression of ZNRF3, and multivariate Cox model demonstrated ZNRF3 as an independent prediction index for overall survival and disease-free survival. In vitro, the overexpression of ZNRF3 was related to the negative regulation of Wnt/β-catenin pathway and referred to an induction of apoptosis and suppression of proliferation in ZNRF3-transfected HCT-116 cells. CONCLUSION: Our results suggest that the higher expression of ZNRF3 acts as a novel marker of indicating the optimistic prognosis of colorectal carcinoma by suppressing cancer cell growth and facilitating apoptosis.