High Expression of Glypican-1 Predicts Dissemination and Poor Prognosis in Glioblastomas

World Neurosurg. 2017 Sep:105:282-288. doi: 10.1016/j.wneu.2017.05.165.

Abstract

Objective: Glioblastoma (GBM) relapses locally or in a disseminated pattern and is highly resistant to chemoradiotherapy. Although dissemination is associated with poor prognosis for patients with GBM, the clinicopathologic factors that promote dissemination have not been elucidated. Glypican-1 (GPC-1) is a heparin sulfate proteoglycan that is attached to the extracytoplasmic surface of the cell membrane and regulates cell motility. The aim of this study was to determine whether GPC-1 expression correlated with GBM dissemination and patient prognosis.

Methods: GPC-1 expression was examined by immunohistochemistry in 53 patients with GBM who received radiotherapy and temozolomide treatment. We assessed the relationship between dissemination and clinicopathologic factors, including GPC-1 expression. We also evaluated the relationship between GPC-1 expression and overall survival (OS) by uni- and multivariate analyses of a range of clinicopathologic factors, including age, Karnofsky Performance Status, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) status.

Results: Logistic regression analysis revealed that GPC-1 expression correlated with dissemination (P = 0.0116). Log-rank tests revealed that age, Karnofsky Performance Status, extent of resection, MGMT status, dissemination (P = 0.0008) and GPC-1 expression (P = 0.0011) were significantly correlated with OS. Multivariate analysis indicated that age, MGMT status, and GPC-1 expression were significantly correlated with OS. GPC-1 expression had the highest hazard ratio (2.392) among all regressors.

Conclusions: GPC-1 expression significantly correlated with OS in patients with GBM who received radiotherapy and temozolomide treatment. GPC-1 expression can help predict the occurrence of dissemination and shorter OS in patients with GBM.

Keywords: Dissemination; Glioblastoma; Glypican-1; Prognosis; Radiotherapy; Temozolomide.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain / metabolism*
  • Brain / pathology
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / radiotherapy
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / metabolism
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Disease Progression
  • Female
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Glioblastoma / radiotherapy
  • Glypicans / metabolism*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Karnofsky Performance Status
  • Ki-67 Antigen / metabolism
  • Logistic Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Retrospective Studies
  • Temozolomide
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • GPC1 protein, human
  • Glypicans
  • Ki-67 Antigen
  • Tumor Suppressor Proteins
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide