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

## TL;DR

This study identifies RNF43 and AXIN2 as potential biomarkers for better survival in gastric cancer patients, while HUNK is linked to worse outcomes.

## Contribution

The study identifies RNF43 co-expressors and their prognostic significance in gastric cancer for the first time.

## Key findings

- High RNF43 expression is associated with prolonged overall survival in gastric cancer patients.
- AXIN2 co-expression with RNF43 further improves patient survival outcomes.
- Overexpression of HUNK alone is linked to poor prognosis, but combined with RNF43 it improves survival.

## Abstract

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.