Progranulin overexpression predicts overall survival in patients with glioblastoma

Abstract

Despite multimodal treatment, patients with astrocytoma still face a poor survival, and identification of valuable prognostic factors is crucial to yield effective individual therapy strategies. The aim of this study was to investigate progranulin (PGRN) expression in astrocytomas and explore its association with tumor grade and overall patient survival by scoring the PGRN immunoreactivity of both tumor cells and blood vessels. About 210 astrocytoma samples with different WHO grades and 14 normal brain tissues were studied by immunohistochemistry for PGRN. Semi-quantitative RT-PCR and Western blot were carried out to confirm its expression in 35 tumor specimens. Serum levels of PGRN in glioblastoma were examined by enzyme immunometric assay. PGRN expression was almost undetectable in the normal brain tissues by immunohistochemistry but increased in both astrocytoma cells and tumor blood vessels with pathological grading. Sera in glioblastoma were significantly higher than in healthy control. In grade II astrocytoma, strong vascular PGRN expression was closely related to tumor recurrence. In glioblastoma, high total PGRN expression, strong vascular PGRN expression, and strong tumor cellular PGRN expression all correlated with decreased patient survival in univariate analysis. However, only total PGRN expression as well as vascular PGRN expression status was independently associated with patient's survival in the multivariate analysis. These results suggest that PGRN, involved in astrocytoma progression, may serve as a prognostic biomarker for glioblastoma.