title: Serum alpha 2-HS glycoprotein predicts survival in patients with glioblastoma.
abstract: BACKGROUND
  Glioblastoma, the most common primary brain tumor, has variable prognosis. We aimed to identify serum biomarkers that predict survival of patients with glioblastoma.
  
  
  METHODS
  In phase 1 (biomarker discovery), SELDI-TOF mass spectra were studied in 200 serum samples from 58 control subjects and 36 patients with grade II astrocytoma, 15 with anaplastic astrocytoma, and 91 with glioblastoma. To identify potential biomarkers, we searched for peptide peaks that changed progressively in size with increasing malignancy. One peak, identified as the B-chain of alpha 2-Heremans-Schmid glycoprotein (AHSG), was less prominent with increasing tumor grade. We therefore investigated AHSG as a survival predictor in glioblastoma. We measured serum AHSG by turbidimetry and determined indices of malignancy, including tumor proliferation (Ki67 immunolabel) and necrosis (tumor lipids on magnetic resonance spectroscopy). In phase 2 (biomarker validation), the prognostic power of AHSG was validated in an independent group of 72 glioblastoma patients.
  
  
  RESULTS
  Median survival was longer (51 vs 29 weeks) in glioblastoma patients with normal vs low serum AHSG concentrations (hazard ratio 2.7, 95% CI 1.5-5.0, P <0.001), independent of age and Karnofsky score. Serum AHSG inversely correlated with Ki-67 immunolabeling and tumor lipids. A prognostic index combining serum AHSG with patient age and Karnofsky score separated glioblastoma patients with short (<3 months) and long (>2 years) median survival. The prognostic value of serum AHSG was validated in a different cohort of glioblastoma patients.
  
  
  CONCLUSIONS
  We conclude that serum AHSG concentration, measured before starting treatment, predicts survival in patients with glioblastoma.
authors.affiliation: Academic Neurosurgery Unit, St. George's University of London, Cranmer Terrace, London, UK.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Petrik
authors.forename: Samira
authors.initials: S
authors.lastname: Saadoun
authors.forename: Alison
authors.initials: A
authors.lastname: Loosemore
authors.forename: Josie
authors.initials: J
authors.lastname: Hobbs
authors.forename: Kirstie S
authors.initials: KS
authors.lastname: Opstad
authors.forename: Joanna
authors.initials: J
authors.lastname: Sheldon
authors.forename: Edward
authors.initials: E
authors.lastname: Tarelli
authors.forename: Franklyn A
authors.initials: FA
authors.lastname: Howe
authors.forename: B Anthony
authors.initials: BA
authors.lastname: Bell
authors.forename: Marios C
authors.initials: MC
authors.lastname: Papadopoulos
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein