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Clinical Chemistry 54: 713-722, 2008. First published February 15, 2008; 10.1373/clinchem.2007.096792
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Right arrow Proteomics and Protein Markers
(Clinical Chemistry. 2008;54:713-722.)
© 2008 American Association for Clinical Chemistry, Inc.

Proteomics and Protein Markers

Serum {alpha}2-HS Glycoprotein Predicts Survival in Patients with Glioblastoma

Vladimir Petrik1, Samira Saadoun1, Alison Loosemore1, Josie Hobbs2, Kirstie S. Opstad4, Joanna Sheldon2, Edward Tarelli3, Franklyn A. Howe4, B. Anthony Bell1 and Marios C. Papadopoulos1,a

1 Academic Neurosurgery Unit, 2 Protein Reference Unit, 3 Medical Biomics Centre, and 4 Biomedical Magnetic Resonance Research Group, St. George’s University of London, Cranmer Terrace, London, U.K.

aAddress correspondence to this author at: Academic Neurosurgery Unit, Jenner Wing Room 1.122, St. George’s University of London, Cranmer Terrace, London, SW17 0RE, UK. Fax +44–20-87255139; e-mail mpapadop{at}sgul.ac.uk.

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.






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