Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients
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Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients. / Mock, Andreas; Warta, Rolf; Geisenberger, Christoph; Bischoff, Ralf; Schulte, Alexander; Lamszus, Katrin; Stadler, Volker; Felgenhauer, Thomas; Schichor, Christian; Schwartz, Christoph; Matschke, Jakob; Jungk, Christine; Ahmadi, Rezvan; Sahm, Felix; Capper, David; Glass, Rainer; Tonn, Jörg-Christian; Westphal, Manfred; von Deimling, Andreas; Unterberg, Andreas; Bermejo, Justo Lorenzo; Herold-Mende, Christel.
In: ONCOTARGET, Vol. 6, No. 15, 12.04.2015, p. 13576-13590.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Printed peptide arrays identify prognostic TNC serumantibodies in glioblastoma patients
AU - Mock, Andreas
AU - Warta, Rolf
AU - Geisenberger, Christoph
AU - Bischoff, Ralf
AU - Schulte, Alexander
AU - Lamszus, Katrin
AU - Stadler, Volker
AU - Felgenhauer, Thomas
AU - Schichor, Christian
AU - Schwartz, Christoph
AU - Matschke, Jakob
AU - Jungk, Christine
AU - Ahmadi, Rezvan
AU - Sahm, Felix
AU - Capper, David
AU - Glass, Rainer
AU - Tonn, Jörg-Christian
AU - Westphal, Manfred
AU - von Deimling, Andreas
AU - Unterberg, Andreas
AU - Bermejo, Justo Lorenzo
AU - Herold-Mende, Christel
PY - 2015/4/12
Y1 - 2015/4/12
N2 - 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.t('bib99');return true;">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.
AB - 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.t('bib99');return true;">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.
U2 - 10.18632/oncotarget.3791
DO - 10.18632/oncotarget.3791
M3 - SCORING: Journal article
C2 - 25944688
VL - 6
SP - 13576
EP - 13590
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 15
ER -