Glioma prognosis is shaped by molecular markers such as IDH mutation, WHO grade, and MGMT methylation, yet heterogeneity persists within defined subgroups. Sidekick Cell Adhesion Molecule 1 (SDK1), an immunoglobulin superfamily member mediating homophilic adhesion, has been documented in glioma tissue but lacks systematic prognostic evaluation. I assessed SDK1’s prognostic value using the Chinese Glioma Genome Atlas (CGGA, N = 503) and The Cancer Genome Atlas (TCGA, N = 572) through multivariate Cox regression, subgroup analyses, differential gene expression, pathway enrichment, ssGSEA-based immune profiling, and molecular subtype association. High SDK1 expression was independently associated with poor overall survival in both cohorts (CGGA: adjusted HR = 1.48, 95% CI 1.16–1.89, p = 0.002; TCGA: HR = 1.76, 95% CI 1.19–2.61, p = 0.005; pooled HR = 1.55, I2 = 0%). Effect estimates varied across subgroups, with significant associations in WHO grade IV and IDH-wildtype strata but not in grade II or older patients. Cross-validated differentially expressed genes were enriched in extracellular matrix organization and focal adhesion pathways. Notably, SDK1 expression showed weak but statistically significant correlations with COL1A1-associated mesenchymal program scores (CGGA: R = 0.12, p = 0.008; TCGA: R = 0.15, p 0.05). SDK1 is a candidate prognostic biomarker in glioma co-occurring with ECM remodeling and immunosuppressive features, warranting experimental validation for clinical translation.
Jun Hyun Lee (Fri,) studied this question.