Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients
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Andreas Mock1, Rolf Warta1, Christoph Geisenberger1, Ralf Bischoff2,3, Alexander Schulte4, Katrin Lamszus4, Volker Stadler2, Thomas Felgenhauer2, Christian Schichor5, Christoph Schwartz5, Jakob Matschke6, Christine Jungk1, Rezvan Ahmadi1, Felix Sahm7,8, David Capper7,8, Rainer Glass5, Jörg-Christian Tonn5, Manfred Westphal4, Andreas von Deimling7,8, Andreas Unterberg1, Justo Lorenzo Bermejo9,10 and Christel Herold-Mende1
1 Department of Neurosurgery, Experimental Neurosurgery, University of Heidelberg, Heidelberg, Germany
2 PEPperPRINT GmbH, Heidelberg, Germany
3 Division of Functional Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg, Germany
4 Department of Neurosurgery, Laboratory for Brain Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5 Department of Neurosurgery, Klinikum Grosshadern, Ludwigs-Maximilians-University, Munich, Germany
6 Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
7 Department of Neuropathology, Institute of Pathology, Heidelberg, Germany
8 Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
9 Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
10 Research Group Molecular Genetics of Breast Cancer, German Cancer Research Centre (DKFZ), Heidelberg, Germany
Christel Herold-Mende , email:
Keywords: glioblastoma, serum, antibodies, long-term survival, TNC, non-invasive biomarker
Received: January 13, 2015 Accepted: March 18, 2015 Published: April 12, 2015
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.
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