SDK1 as an Independent Prognostic Biomarker in Primary Glioma: A Multi-Cohort Validation Study with Functional...

Area of Science:

• Neuro-oncology
• Molecular Biology
• Cancer Genomics

Background:

• Glioma prognosis relies on markers like IDH mutation and WHO grade, but patient subgroups show persistent heterogeneity.
• Sidekick Cell Adhesion Molecule 1 (SDK1), involved in cell adhesion, is present in glioma but its prognostic role is unevaluated.

Purpose of the Study:

• To investigate the prognostic value of Sidekick Cell Adhesion Molecule 1 (SDK1) expression in glioma.
• To explore the association of SDK1 with molecular subtypes, pathway enrichment, and immune microenvironment in glioma.

Main Methods:

• Utilized multivariate Cox regression and subgroup analyses on Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) cohorts (N=503 and N=572).
• Performed differential gene expression, pathway enrichment analysis, ssGSEA-based immune profiling, and correlation with molecular subtypes and gene signatures.
• Assessed the independence of SDK1's prognostic significance from tumor mutational burden (TMB).

Main Results:

• High SDK1 expression was an independent predictor of poor overall survival in both CGGA (HR=1.48) and TCGA (HR=1.76) cohorts.
• Significant associations were observed in WHO grade IV and IDH-wildtype gliomas, with enrichment in extracellular matrix organization and focal adhesion pathways.
• SDK1 expression correlated with mesenchymal invasion programs and was associated with M2 macrophage and Treg signatures, alongside upregulated immune checkpoints.

Conclusions:

• SDK1 is a candidate prognostic biomarker for glioma, independent of TMB.
• Its expression is linked to extracellular matrix remodeling and an immunosuppressive tumor microenvironment.
• Further experimental validation is recommended for potential clinical translation of SDK1 as a prognostic tool.