Abstract
Gliomas are primary brain tumors with high mortality and heterogeneous biology that is insufficiently understood. In this study, we performed a systematic analysis of the intrinsic organization of complex glioma transcriptome to gain deeper knowledge of the tumor biology. Gene coexpression relationships were explored in 790 glioma samples from 5 published patient cohorts treated at different institutions. We identified 20 coexpression modules that were common to all the data sets and associated with proliferation, angiogenesis, hypoxia, immune response, genomic alterations, cell differentiation phenotypes, and other features inherent to glial tumors. A collection of high-quality signatures for the respective processes was obtained using cross-data set summarization of the modules' gene composition. Individual modules were found to be organized into higher order coexpression groups, the two largest of them associated with glioblastoma and oligodendroglioma, respectively. We identified a novel prognostic gene expression signature (185 genes) linked to a proastrocytic pattern of tumor cell differentiation. This "proastrocytic" signature was associated with long survival and defined a subgroup of the previously established "proneural" class of gliomas. A strong negative correlation between proastrocytic and proneural markers across differentiated tumors underscored the distinction between these subtypes of glioma. Interestingly, one further novel signature in glioma was identified that was associated with EGFR (epidermal growth factor receptor) gene amplification and suggested that EGF signaling in glioma may be a subject to regulation by Sprouty family proteins. In summary, this integrated analysis of the glioma transcriptome provided several novel insights into molecular heterogeneity and pathogenesis of glial tumors.
Highlights
Gliomas are the most common primary brain tumors in adults [1]
Gliomas are classified into 2 major subtypes: astrocytoma and oligodendroglioma [1], which are further divided into grades ranging from I to IV accord
Our results suggest a functional link between Sprouty proteins and oncogenic epidermal growth factor receptor (EGFR) signaling in glioma
Summary
Gliomas are the most common primary brain tumors in adults [1]. Despite advances in their surgery, radiotherapy, and chemotherapy, the majority of gliomas remain lethal within 1 to 3 years from the time of diagnosis [2]. A key challenge for diagnosing and treatment of glial tumors is their high interindividual heterogeneity [3]. Gliomas are classified into 2 major subtypes: astrocytoma and oligodendroglioma [1], which are further divided into grades ranging from I (benign tumors) to IV (malignant glioblastoma) accord-. Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/). The results published here are in part based on data generated by the Glioma Molecular Diagnostic Initiative project
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
