Increased HSPG2 expression independently predicts poor survival in patients with oligoastrocytoma and oligodendroglioma.

Abstract

Perlecan, which is also called heparan sulfate proteoglycan 2 (HSPG2), is a protein encoded by the HSPG2 gene that maps to 1p36.12 in the human genome. In this study, we assessed the independent prognostic value of HSPG2 in terms of overall survival (OS) and recurrence-free survival (RFS) in patients with LGG. A retrospective study was conducted by using data in the Cancer Genome Atlas-Low Grade Glioma (TCGA-LGG). Increased HSPG2 expression was an independent prognostic indicator of poor OS in oligoastrocytoma (HR: 1.644, 95% CI: 1.116-2.423, p = 0.012) and in oligodendroglioma (HR: 1.459, 95% CI: 1.138-1.871, p = 0.003). In addition, increased HSPG2 expression independently predicted poor RFS in oligodendroglioma (HR: 1.402, 95% CI: 1.110-1.770, p = 0.005). Furthermore, we observed that high HSPG2 expression was associated with significantly shorter OS and RFS in oligodendroglioma, no matter the patients received radiotherapy or not. Using copy number alterations (CNAs) and DNA methylation data in TCGA-LGG, we found that DNA copy deletion was generally associated with decreased HSPG2 expression. Regression analysis suggested a weak negative correlation between HSPG2 expression and HSPG2 DNA methylation (Pearson's r = -0.388). Increased HSPG2 expression could independently predict poor OS in oligoastrocytoma and oligodendroglioma and also independently predicted poor RFS in oligodendroglioma. Its expression is modulated by both DNA copy number and DNA methylation in oligodendroglioma.