The Prognostic Impact of Canonical and Non-Canonical Wnt Signaling in Solid Tumours: A Systematic Review and Meta-Analysis

Background: The canonical Wnt signaling pathway regulates cell proliferation, differentiation and immune modulation in cancer. While β-catenin is well studied, the prognostic impact of broader Wnt-related markers remains unclear across tumour types. Methods: We conducted a systematic review and meta-analysis of studies evaluating the association between Wnt signaling components and survival outcomes in solid tumours. Databases searched included PubMed, Embase and the Cochrane Library. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using random-effects models. Subgroup analyses were performed by cancer type, disease stage and biomarker. Results: Twenty-two studies met inclusion criteria. Among Wnt-related biomarkers, elevated β-catenin expression showed the strongest association with reduced OS in colorectal, gastric and hepatocellular cancers (pooled HR: 2.37; 95% CI: 1.89–3.45). Overexpression of other Wnt modulators including DKK1, EpCAM and SFRP4 was also consistently linked to poor prognosis, immune evasion and tumour progression. DKK1 in biliary tract cancers and EpCAM in colorectal cancers were significantly associated with worse PFS. Subgroup analyses revealed higher HRs in advanced-stage disease (HR: 3.12; 95% CI: 2.14–4.01) compared to early-stage cancers (HR: 1.85; 95% CI: 1.33–2.52). Conclusion: This pan-cancer meta-analysis highlights the adverse prognostic role of canonical and non-canonical Wnt pathway components. Our findings support the clinical utility of β-catenin, DKK1, EpCAM and SFRP4 as candidate biomarkers for risk stratification and as potential therapeutic targets for Wnt-directed strategies.