ATP-Binding Cassette Transporter Expression and Methylation Profiles as Potential Biomarkers in Glioma

Gliomas are malignant central nervous system tumors characterized by poor prognosis and therapy failure. Adenosine triphosphate-binding cassette (ABC) transporters mediate multidrug resistance via chemotherapeutic efflux, yet their roles as biomarkers across glioma subtypes remain unclear. We analyzed adult diffuse glioma mRNA expression (n = 693; n = 325) and DNA methylation (n = 159) datasets from the Chinese Glioma Genome Atlas in silico, stratifying samples according to the 2021 World Health Organization molecular criteria. ABC transporter profiles, patient-matched methylation–expression correlations (n = 26 overlapping patients; 78 paired gene–sample observations), and prognostic values were evaluated using non-parametric tests with false discovery rate (FDR) correction, Kaplan–Meier curves, and multivariable Cox proportional-hazards regression analyses. Transporter expression and methylation varied significantly by histology and grade. ABCC1 expression increased with malignancy, predicting worse overall survival in univariable analysis (p < 0.0001). Meanwhile, strongly correlated ABCB1 and ABCG2 expressions (Spearman’s ρ = 0.80 in grade 4 tumors) were higher in lower-grade gliomas. Progressive hypomethylation occurred with increasing grade, with significant differential methylation in ABCB1 (FDR p < 0.0001) and ABCG2 (FDR p < 0.0001). In patient-matched integrative analyses, only ABCC1 exhibited a significant inverse association between methylation and expression (Spearman’s ρ = −0.58, p = 0.0019). Baseline clinical multivariable Cox regression (n = 139) suggested that higher ABCB1 and ABCG2 methylation (HR = 0.11, p = 0.03; HR = 0.12, p = 0.04 per 1.0-unit β increase, corresponding to HR = 0.80 and 0.81 per 0.1-unit β increase) may act as protective factors independent of age and grade (though attenuated upon IDH adjustment), whereas higher grade and ABCG2 expression (n = 542; HR = 1.03, p = 0.001) emerged as independent risk factors. Specific ABC transporter profiles could serve as candidate prognostic biomarkers in glioma, warranting external and translational validation.