WNT5A in Cancer: A Pan-Cancer Analysis Revealing Its Diagnostic and Prognostic Biomarker Potential

Background and objective: The wingless-related integration site family (WNT) signaling pathway is critical for tumor progression and development. It is associated with various neoplasms produced by WNT pathway deregulation; WNT5A, a member of the WNT family, has been linked to carcinogenesis, exhibiting either oncogenic or tumor-suppressive effects. The study investigates how the gene affects certain types of cancer. The study aimed to evaluate the potential prognostic significance of WNT5A genes as diagnostic biomarkers for various types of cancer. Methodology: We investigated WNT5A gene expression in a pan-cancer analysis using various bioinformatics databases, including GEPIA (Gene Expression Profiling Interactive Analysis), TIMER2 (Tumor Immune Estimation Resource, Version 2), the University of Alabama at Birmingham Cancer Data Analysis Portal UACLAN databases, the Kaplan-Meier (K-M) plotter, cBioPortal, and Gene Set Cancer Analysis (GSCA). We aimed to gain insight into the expression of WNT5A in various tumors and its relationship with immune infiltration, overall survival, and genetic changes. Public datasets validated WNT5A expression in lung squamous cell carcinoma (LUSC) and stomach adenocarcinoma (STAD) samples. Results: WNT5A pan-cancer analysis was highly expressed in two cancer types, including STAD and LUSC. Additionally, TIMER results showed a positive association of WNT5A with immune cell infiltration in LUSC and STAD. Survival analysis indicated that LUSC cancer exhibits better overall survival, while STAD has lower overall survival levels, which means a poor prognosis in the STAD cancer type. Furthermore, mutation analysis revealed that the WNT5A gene was mutated in 1.4% of cases, with most alterations being deletions followed by amplifications. Conclusions: The WNT5A gene's high expression in many malignancies, including LUSC and STAD, suggests it could be used as a diagnostic biomarker. This study shows a relationship between WNT5A expression and immune cell abundance in LUSC and STAD. Our pan-cancer analysis of this gene is the first of its type, and it will inform future research, comprehensive investigation, and wet lab experiments.