Definition of a serum marker panel for glioblastoma discrimination and identification of Interleukin 1β in the microglial secretome as a novel mediator of endothelial cell survival induced by C-reactive protein.

摘要: Glioblastoma (GBM) is the most common malignant adult primary brain tumor. We profiled 724 cancer-associated proteins in sera of healthy individuals (n = 27) and GBM 28) using antibody microarray. While 69 exhibited differential abundance sera, a three-marker panel (LYAM1, BHE40 CRP) could discriminate from that donors with an accuracy 89.7% p < 0.0001. The high C-reactive protein (CRP) was confirmed 264 independent samples. High levels CRP seen but without change transcript suggesting non-tumoral origin. Glioma-secreted Interleukin 6 (IL6) found to induce hepatocytes secrete CRP, involving JAK-STAT pathway. culture supernatant CRP-treated microglial cells induced endothelial cell survival under nutrient-deprivation condition CRP-Fc gamma RIII signaling cascade. Transcript profiling identified 1 beta (IL1 beta) present secretome as key mediator CRP-induced survival. IL1 neutralization by antibody-binding or siRNA-mediated silencing reduced ability Thus our study identifies serum based for diagnosis provides leads developing targeted therapies. Biological significance A complex microarray marker - LYAM1, accurate discriminator glioblastoma individuals. concomitant increase transcripts glioblastoma. IL6 produce dependent manner. release which turn promoted This study, besides defining discrimination, potential candidate therapy. (C) 2015 Elsevier B.V. All rights reserved.