{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:04:59Z","timestamp":1784613899134,"version":"3.55.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Siglec-15 has emerged as a novel immune checkpoint molecule and a potential therapeutic target in solid tumors. Previous studies reported inconsistent prognostic significance of tumoral Siglec-15 expression across cancer types. We therefore conducted a systematic review and meta-analysis to comprehensively evaluate the association of tumoral Siglec-15 expression with survival outcomes in patients with solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Web of Science, and EMBASE were systematically searched from database inception to March 30, 2026. Observational studies investigating Siglec-15 protein expression in tumor cells and prognosis were included. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were applied to calculate pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Prespecified subgroup analyses, meta-regression analyses, and publication bias assessment were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-seven datasets involving 4075 patients were included. High tumoral Siglec-15 expression was significantly associated with poorer overall survival (OS, HR\u00a0=\u00a01.53, 95% CI: 1.25-1.86,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and worse disease-free\/recurrence-free survival (DFS\/RFS, HR\u00a0=\u00a01.30, 95% CI: 1.09-1.55,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.004). No significant association was observed for progression-free survival (HR\u00a0=\u00a01.03, 95% CI: 0.67-1.56,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.903). High Siglec-15 expression showed a marginal association with improved disease-specific survival (DSS, HR\u00a0=\u00a00.66, 95% CI: 0.43-1.00,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.050). Tumor-specific analyses demonstrated significantly worse OS in colorectal cancer, gastric cancer, and osteosarcoma, whereas breast cancer showed a non-significant association in the opposite direction (HR\u00a0=\u00a00.72, 95% CI: 0.33-1.56). Tumoral Siglec-15 expression was inversely associated with PD-L1 positivity (OR\u00a0=\u00a00.40, 95% CI: 0.23-0.72,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.002), supporting a mutually exclusive immune checkpoint pattern. No significant associations were observed between Siglec-15 expression and most clinicopathological features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated tumoral Siglec-15 expression was associated with unfavorable OS and DFS\/RFS, whereas the borderline association with improved DSS should be interpreted cautiously because it was based on only three studies. These findings support a highly cancer-type dependent role of Siglec-15 as a clinically relevant prognostic biomarker and a promising immunotherapeutic target. Further prospective studies are needed to validate these findings and develop standardized assessment strategies, preferably using fixed cutoff values and simplified scoring methods.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1905631","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:34:55Z","timestamp":1784612095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic significance of tumoral Siglec-15 expression in solid tumors: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Ningning","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Oncology, Heping Hospital Affiliated to Changzhi Medical College","place":["Changzhi, Shanxi, 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