Abstract

BackgroundGlioblastoma (GB) is the most common and aggressive tumor of the brain. Genotype-based approaches and independent analyses of the transcriptome or the proteome have led to progress in understanding the underlying biology of GB. Joint transcriptome and proteome profiling may reveal new biological insights, and identify pathogenic mechanisms or therapeutic targets for GB therapy. We present a comparison of transcriptome and proteome data from five GB biopsies (TZ) vs their corresponding peritumoral brain zone (PBZ). Omic analyses were performed using RNA microarray chips and the isotope-coded protein label method (ICPL).ResultsAs described in other cancers, we found a poor correlation between transcriptome and proteome data in GB. We observed only two commonly deregulated mRNAs/proteins (neurofilament light polypeptide and synapsin 1) and 12 altered biological processes; they are related to cell communication, synaptic transmission and nervous system processes. This poor correlation may be a consequence of the techniques used to produce the omic profiles, the intrinsic properties of mRNA and proteins and/or of cancer- or GB-specific phenomena. Of interest, the analysis of the transcription factor binding sites present upstream from the open reading frames of all altered proteins identified by ICPL method shows a common binding site for the topoisomerase I and p53-binding protein TOPORS. Its expression was observed in 7/11 TZ samples and not in PBZ. Some findings suggest that TOPORS may function as a tumor suppressor; its implication in gliomagenesis should be examined in future studies.ConclusionsIn this study, we showed a low correlation between transcriptome and proteome data for GB samples as described in other cancer tissues. We observed that NEFL, SYN1 and 12 biological processes were deregulated in both the transcriptome and proteome data. It will be important to analyze more specifically these processes and these two proteins to allow the identification of new theranostic markers or potential therapeutic targets for GB.

Highlights

  • Glioblastoma (GB) is the most common and aggressive tumor of the brain

  • The Western blot analysis of expression of neurofilament light polypeptide (NEFL) and synapsin 1 (SYN1) in a larger cohort of tumor zone (TZ) samples and their corresponding peritumoral brain zone (PBZ) (n = 11) confirmed the transcriptomic results; in most cases, an underexpression of NEFL and SYN1 proteins was observed in the TZ (9/11 for NEFL and 10/11 for SYN1) (Fig. 1)

  • There were few common features in the transcriptome and proteome data: they were the deregulation of two mRNAs/proteins (NEFL and SYN1) and 12 biological processes; they are related to cell communication, synaptic transmission and nervous system processes

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Summary

Introduction

Glioblastoma (GB) is the most common and aggressive tumor of the brain. Genotype-based approaches and independent analyses of the transcriptome or the proteome have led to progress in understanding the underlying biology of GB. Joint transcriptome and proteome profiling may reveal new biological insights, and identify pathogenic mechanisms or therapeutic targets for GB therapy. We present a comparison of transcriptome and proteome data from five GB biopsies (TZ) vs their corresponding peritumoral brain zone (PBZ). Glioblastoma (GB) is the most common and aggressive primary tumor in the adult brain. Progresses have been made in understanding the underlying biology of GB thank to work involving genotype-based approaches and proteome analyses. Genome-wide profiling studies have highlighted the existence of molecular subtypes of GB with distinct biological features and clinical correlates [3,4,5]. Verhaak et al [3] described four subtypes of

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