Serum alpha 2-HS glycoprotein predicts survival in patients with glioblastoma.
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.
Petrik
Vladimir
V
Academic Neurosurgery Unit, St. George's University of London, Cranmer Terrace, London, UK.
Saadoun
Samira
S
Loosemore
Alison
A
Hobbs
Josie
J
Opstad
Kirstie S
KS
Sheldon
Joanna
J
Tarelli
Edward
E
Howe
Franklyn A
FA
Bell
B Anthony
BA
Papadopoulos
Marios C
MC
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
C556354:AHSG protein, human; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein