Bioinformatic Analysis of RNF43 and Its Co-expressors As Prognostic Biomarkers for Gastric Cancer

Background Gastric cancer (GC) exhibits high morbidity and mortality rates worldwide. Although surgery, pharmacotherapy using antibody drugs, and chemotherapy improve the survival rate, some patients exhibit a poor prognosis, necessitating the identification of new prognostic factors. Downregulation or mutation of the ring finger protein (RNF)-43, a negative regulator of the Wnt pathway, serves as a poor prognostic factor for various cancers; however, its specific mechanisms in GC remain unclear. Therefore, in this study, we used a clinical database to determine whether RNF43 and its co-expressors impact the life expectancy of patients with GC. ​Methods The evaluations were executed on publicly available datasets and website for analysis, including the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), cBioPortal, Kaplan-Meier plotter, Linkedomics, and WebGestalt. Results Notably, high RNF43 expression prolonged the overall survival (OS) of patients with GC. AXIN2, zinc and ring finger three (ZNRF3), bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI), and hormonally upregulated Neu-associated kinase (HUNK) were identified as RNF43 co-expressors. Among these, co-expression of ZNRF3 and BAMBI had no impact, whereas co-expression of AXIN2 prolonged the patient's OS. In contrast, overexpression of HUNK alone was associated with a poor prognosis for patients with GC. Moreover, overexpression of both RNF43 and HUNK was associated with prolonged OS compared to the overexpression or unaltered expression of HUNK alone. Conclusion Collectively, these results suggest RNF43 and AXIN2 as favorable prognostic factors and HUNK as a poor prognostic factor and therapeutic target for patients with GC.