The Role of Galectins in Prognosis of Melanoma: A Systematic Review and Meta-Analysis

Abstract

Background: Galectins are a family of carbohydrate-binding proteins that are implicated in various biological processes, including cancer development and progression. This study aimed to evaluate the role of galectins as prognostic markers in patients with melanoma. Methods: We conducted a PRISMA-guided systematic review of PubMed/MEDLINE, Scopus, and Web of Science from inception to November 2025. Eligible studies reported associations between galectin expression (tissue or circulating) and survival outcomes in melanoma with extractable effect estimates. Two reviewers performed screening and data extraction; study quality was appraised with the Newcastle-Ottawa Scale. Random-effects meta-analyses pooled hazard ratios (HRs) and 95 confidence interval (CI) for overall survival (OS) and disease-free or recurrence-free survival (DFS/RFS), with heterogeneity (I²), sensitivity analyses, and small-study effect tests. The meta-analysis was performed using STATA 14.0. Results: Fourteen studies (n = 2,280) met criteria. Higher galectin expression showed no significant association with OS in categorical analyses (pooled HR = 1.32, 95 CI 0.68, 2.58; I²=89.8). DFS/RFS was likewise non-significant (HR = 1.2, 95 CI 0.46, 3.13; I²=58.3). Mortality was not significantly related to galectins with pooled HR = 1.73 (95 CI 0.45, 6.68; I²=89.9). One study reporting a continuous effect suggested improved OS with higher levels (HR = 0.73, 95 CI 0.55, 0.97). Small-study effects were not evident by Egger’s or Begg’s tests. Qualitative synthesis indicated subtype and matrix specificity: galectin-3 was more often linked to adverse pathological features, galectin-1 was largely null for survival, and galectin-9 findings differed between tissue and circulating assays. Plasma Galectin-3 was related to better progression related survival. Conclusion: Pooled data do not support a consistent association between aggregated galectin expression and survival in melanoma. Heterogeneity by galectin subtype, specimen type, assay, and cut-offs likely underlies discrepant findings. Standardized, subtype-specific evaluations in well-designed cohorts are needed to clarify clinical utility. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2026.