ArticleDiscover oncology2025
Elevated expression of SIGLEC8 in skin cutaneous melanoma predicts better prognosis associated with hematopoietic cell lineage pathway.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCutaneous melanoma (SKCM) is becoming more common. Current prognostic markers-TNM stage, BRAF mutation status, and tumor mutational burden (TMB)-do not offer precise predictions. Recent studies point to a key role for the tumor microenvironment. To date, we do not know how SIGLEC8 (a sialic acid-binding immunoglobulin‑like lectin) affects immune regulation or prognosis in SKCM.
methodsWe used logistic regression to link SIGLEC8 expression with clinical and pathological features. We then applied Cox regression and Kaplan‑Meier survival analysis to assess how these features relate to overall survival (OS). For differential genes, we performed Gene Ontology (GO) and KEGG enrichment tests by combining fold‑change thresholds with hypergeometric statistics. Finally, we ran Pearson and Spearman correlations to study the relationship between SIGLEC8 and immune‑infiltration markers.
resultsFrom TCGA, we selected SKCM cases that had both complete clinical records and transcriptome data. We excluded 8.2% of samples due to missing information; this did not introduce any bias in age or sex. Patients with low SIGLEC8 levels tended to have T4 tumors, Breslow depth over 3 mm, ulceration, and more advanced disease (p < 0.05). High SIGLEC8 expression was linked to better OS (p < 0.001) in Cox analysis. This prognostic value held true across subgroups defined by age, gender, BMI, and stage (all p < 0.05). Differential expression analysis highlighted three immune genes-FCER2, CR2, and MS4A1-as strongly correlated with SIGLEC8. These findings point to a role in B‑cell and CD8⁺ T‑cell pathways within the hematopoietic lineage.
conclusionsHigh SIGLEC8 expression predicts longer survival in SKCM. We propose that SIGLEC8 boosts antitumor immunity by influencing B‑cell and T‑cell pathways (including FCER2, CR2, MS4A1, and CD8A/B) in the tumor microenvironment. SIGLEC8 thus shows promise as a low‑cost prognostic biomarker and a potential therapeutic target. Table S1 shows cancer-type-specific prognostic effects for SIGLEC8: in SKCM higher SIGLEC8 expression associates with improved survival, whereas prognostic directionality varies across other tumor types. A pan-cancer comparison revealed cancer-type-specific prognostic effects for SIGLEC8: in SKCM higher SIGLEC8 expression associates with improved survival, whereas prognostic directionality varies across other tumor types.
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