Vol.:(0123456789) 1 3 Journal of Neuro-Oncology https://doi.org/10.1007/s11060-017-2739-7 CLINICAL STUDY Molecular profling of short-term and long-term surviving patients identifes CD34 mRNA level as prognostic for glioblastoma survival Signe Regner Michaelsen 1  · Thomas Urup 1,2  · Lars Rønn Olsen 3  · Helle Broholm 4  · Ulrik Lassen 2  · Hans Skovgaard Poulsen 1,2 Received: 30 September 2017 / Accepted: 29 December 2017 © Springer Science+Business Media, LLC, part of Springer Nature 2018 Abstract Despite extensive treatment, overall survival (OS) for glioblastoma (GBM) remains poor. A small proportion of patients present long survival over 3 years, but the underlying molecular background separating these long-term survivors (LTS) from short-term survivors (STS) are insufciently understood. Accordingly, study aim was to identify independent prognostic biomarkers for survival. Study cohort consisted of 93 primary GBM patients treated with radiation-, chemo- and bevacizumab therapy, among which 14 STS (OS ≤ 12 months) and 6 LTS (OS ≥ 36 months) were identifed, all confrmed being IDH wild- type. RNA expression levels in diagnostic tumor specimen for 792 genes were analyzed by NanoString technology. While no diferences were found with regard to GBM subtype between LTS versus STS, comparative analysis of individual genes identifed 14 signifcantly diferently expressed candidate genes. Univariate analysis in the whole patient cohort found that 12 of these were signifcantly associated with OS, of which increased IFNG, CXCL9, LGALS4, CD34 and decreased MGMT levels remained signifcant associated with prolonged OS in multivariate analysis correcting for known prognostic variables. Validation analyses in an independent dataset from the AVAglio study confrmed CD34 as signifcant in comparative analysis between STS and LTS patients and as an independent prognostic factor. Analysis of this dataset further supported CD34 expression to be associated with improved bevacizumab efcacy, while CD34 immunohistochemistry indicated variation in CD34 expression to result primarily from varying tumor vascularization. Collectively, CD34 expression candidates as a prognostic biomarker in GBM able to identify survival outliers and could also be predictive for efcacy of bevacizumab. Keywords Biomarkers · GBM · NanoString · CD34 · MGMT · LTS Background Glioblastoma (GBM) is a devastating disease with median overall survival (OS) rate under 15 months [1]. However, despite a large proportion of the GBM patient population dying within the frst 12 months from diagnosis, around 15% live past 36 months [1, 2]. Access to a reliable method to predict which patients that will turn into short-term-sur- vivors (STS) and long-term-survivors (LTS) could prove benefcial for both clinical trial design and development of individualized treatment programs for GBM. Patient characteristics reported associated with GBM prognosis includes patient age, performance status (PS), extent of resection, multiple lesion sites and corticosteroids use [2–6]. On the molecular side promoter methylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) gene, inversely correlated to gene expression, has been established as a prognostic marker [7–9]. Also mutation Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11060-017-2739-7) contains supplementary material, which is available to authorized users. * Signe Regner Michaelsen signe.regner.michaelsen@regionh.dk; signerm@gmail.com 1 Department of Radiation Biology, Rigshospitalet, Copenhagen, Denmark 2 Department of Oncology, Rigshospitalet, Copenhagen, Denmark 3 Department of Bio and Health Informatics, Technical University of Denmark, Lyngby, Denmark 4 Department of Pathology, Rigshospitalet, Copenhagen, Denmark