title: Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor.
abstract: Angiogenesis plays a key role in glioblastoma biology and antiangiogenic agents are under clinical investigation with promising results. However, the angiogenic profiles of patients with glioblastoma and their clinical significance are not well understood. Here we characterize the serum angiogenic profile of patients with glioblastoma, and examine the prognostic significance of individual angiogenic factors. Serum samples from 36 patients with glioblastoma were collected on admission and simultaneously assayed for 48 angiogenic factors using protein microarrays. The data were analyzed using hierarchical cluster analysis. Vessel morphology was assessed histologically after immunostaining for the pan-endothelial marker CD31. Tumor samples were also immunostained for tissue inhibitor of metalloproteinase-1 (TIMP-1). Cluster analysis of the serum angiogenic profiles revealed 2 distinct subtypes of glioblastoma. The 2 subtypes had markedly different tumor microvessel densities. A low serum level of TIMP-1 was associated with significantly longer survival independent of patient age, performance status, or treatment. The serum angiogenic profile in patients with glioblastoma mirrors tumor biology and has prognostic value. Our data suggest the serum TIMP-1 level as an independent predictor of survival.
authors.affiliation: Academic Neurosurgery Unit, Room 1.122 Jenner Wing, St George's University of London, Cranmer Terrace, Tooting, London SW17 0RE. mjncrocker@gmail.com
authors.forename: Matthew
authors.initials: M
authors.lastname: Crocker
authors.forename: Sue
authors.initials: S
authors.lastname: Ashley
authors.forename: Ian
authors.initials: I
authors.lastname: Giddings
authors.forename: Vladimir
authors.initials: V
authors.lastname: Petrik
authors.forename: Anthea
authors.initials: A
authors.lastname: Hardcastle
authors.forename: Wynne
authors.initials: W
authors.lastname: Aherne
authors.forename: Andy
authors.initials: A
authors.lastname: Pearson
authors.forename: B Anthony
authors.initials: BA
authors.lastname: Bell
authors.forename: Stergios
authors.initials: S
authors.lastname: Zacharoulis
authors.forename: Marios C
authors.initials: MC
authors.lastname: Papadopoulos
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000098:blood supply / Q000145:classification* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000145:classification* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood*; D040081:Protein Array Analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D019715:Tissue Inhibitor of Metalloproteinase-1