title: Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients.
abstract: Liquid biopsies come of age offering unexploited potential to monitor and react to tumor evolution. We developed a cost-effective assay to non-invasively determine the immune status of glioblastoma (GBM) patients. Employing newly developed printed peptide microarrays we assessed the B-cell response against tumor-associated antigens (TAAs) in 214 patients. Firstly, sera of long-term (36+ months, LTS, n=10) and short-term (6-10 months, STS, n=14) surviving patients were screened for prognostic antibodies against 1745 13-mer peptides covering known TAAs (TNC, EGFR, GLEA2, PHF3, FABP5, MAGEA3). Next, survival associations were investigated in two retrospective independent multicenter validation sets (n=61, n=129, all IDH1-wildtype). Reliability of measurements was tested using a second array technology (spotted arrays). LTS/STS screening analyses identified 106 differential antibody responses. Evaluating the Top30 peptides in validation set 1 revealed three prognostic peptides. Prediction of TNC peptide VCEDGFTGPDCAE was confirmed in a second set (p=0.043, HR=0.66 [0.44-0.99]) and was unrelated to TNC protein expression. Median signals of printed arrays correlated with pre-synthesized spotted microarrays (p<0.0002, R=0.33). Multiple survival analysis revealed independence of age, gender, KPI and MGMT status. We present a novel peptide microarray immune assay that identified increased anti-TNC VCEDGFTGPDCAE serum antibody titer as a promising non-invasive biomarker for prolonged survival.
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mock
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Warta
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Geisenberger
authors.affiliation: PEPperPRINT GmbH, Heidelberg, Germany.|Division of Functional Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bischoff
authors.affiliation: Department of Neurosurgery, Laboratory for Brain Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schulte
authors.affiliation: Department of Neurosurgery, Laboratory for Brain Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lamszus
authors.affiliation: PEPperPRINT GmbH, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Stadler
authors.affiliation: PEPperPRINT GmbH, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Felgenhauer
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwigs-Maximilians-University, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schichor
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwigs-Maximilians-University, Munich, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwartz
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Matschke
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Jungk
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Rezvan
authors.initials: R
authors.lastname: Ahmadi
authors.affiliation: Department of Neuropathology, Institute of Pathology, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.affiliation: Department of Neuropathology, Institute of Pathology, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwigs-Maximilians-University, Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Glass
authors.affiliation: Department of Neurosurgery, Klinikum Grosshadern, Ludwigs-Maximilians-University, Munich, Germany.
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.affiliation: Department of Neurosurgery, Laboratory for Brain Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.affiliation: Department of Neuropathology, Institute of Pathology, Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Unterberg
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.|Research Group Molecular Genetics of Breast Cancer, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Justo Lorenzo
authors.initials: JL
authors.lastname: Bermejo
authors.affiliation: Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000737:chemistry*; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D016019:Survival Analysis
chemical_list: D001323:Autoantibodies; D009842:Oligopeptides
keywords: TNC; antibodies; glioblastoma; long-term survival; non-invasive biomarker; serum