Reduction of α-dystroglycan expression is correlated with poor prognosis in glioma

Abstract

Dystroglycan (DG), a multifunctional protein dimer of non-covalently linked α and β subunits, is best known as an adhesion and transduction molecule linking the cytoskeleton and intracellular signaling pathways to extracellular matrix proteins. Loss of DG binding, possibly by degradation or disturbed glycosylation, has been reported in a variety of cancers. DG is abundant at astroglial endfeet forming the blood-brain barrier (BBB) and glia limitans; so, we examined if loss of expression is associated with glioma. Expression levels of α-DG and β-DG were assessed by immunohistochemistry in a series of 78 glioma specimens to determine the relationship with tumor grade and possible prognostic significance. α-DG immunostaining was undetectable in 44 of 49 high-grade specimens (89.8%) compared to 15 of 29 low-grade specimens (51.72%) (P<0.05). Moreover, loss of α-DG expression was an independent predictor of shorter disease-free survival (DFS) (hazards ratio (HR) = 0.142, 95% confidence interval (CI) 0.033-0.611, P=0.0088). Reduced expression of both α-DG and β-DG was also a powerful negative prognostic factor for DFS (HR=2.556, 95% CI 1.403-4.654, P=0.0022) and overall survival (OS) (HR=2.193, 95% CI 1.031-4.666, P=0.0414). Lack of α-DG immunoreactivity is more frequent in high-grade glioma and is an independent predictor of poor clinical outcome. Similarly, lack of both α-DG and β-DG immunoreactivity is a strong independent predictor of clinical outcome.