Objective:

To evaluate the association of tumoral Siglec-15 expression with survival outcomes in patients with solid tumors.

Approach:

• Data Sources: Systematic search of PubMed, Web of Science, and EMBASE from inception to March 30, 2026.
• Study Inclusion: Included observational studies investigating Siglec-15 protein expression in tumor cells and prognosis.
• Quality Assessment: Study quality assessed using the Newcastle-Ottawa Scale.
• Statistical Analysis: Random-effects models used to calculate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs).
• Subgroup Analyses: Prespecified subgroup analyses, meta-regression analyses, and publication bias assessment performed.

Key Findings:

• High tumoral Siglec-15 expression associated with poorer overall survival (OS, HR = 1.53, 95% CI: 1.25-1.86, P < 0.001) and worse disease-free/recurrence-free survival (DFS/RFS, HR = 1.30, 95% CI: 1.09-1.55, P = 0.004).
• No significant association for progression-free survival (HR = 1.03, 95% CI: 0.67-1.56, P = 0.903).
• Marginal association with improved disease-specific survival (DSS, HR = 0.66, 95% CI: 0.43-1.00, P = 0.050).
• Significantly worse OS in colorectal cancer, gastric cancer, and osteosarcoma; non-significant association in breast cancer (HR = 0.72, 95% CI: 0.33-1.56).
• Inversely associated with PD-L1 positivity (OR = 0.40, 95% CI: 0.23-0.72, P = 0.002).

Interpretation:

Limitations:

• Findings based on observational studies which may have inherent biases related to study design and data collection.
• Borderline association with DSS based on only three studies.

Conclusion:

Further prospective studies are needed to validate findings and develop standardized assessment strategies for Siglec-15.