Clinical Chemistry
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Clinical Chemistry 0: clinchem.2007.096792v1, 2008; 10.1373/clinchem.2007.096792
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Received on December 20, 2007
Accepted on January 28, 2008

Proteomics and Protein Markers

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

Vladimir Petrik 1, Samira Saadoun 1, Alison Loosemore 1, Josie Hobbs 2, Kirstie S. Opstad 3, Joanna Sheldon 2, Edward Tarelli 4, Franklyn A. Howe 3, B. Anthony Bell 1, Marios C. Papadopoulos 1*

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

* To whom correspondence should be addressed. 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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Copyright © 2008 by the American Association for Clinical Chemistry.