Department of Neurosurgery, CHU Angers, University Hospital of Angers, 4, Rue Larrey, 49933, Angers Cedex 09, France.
CRCINA, INSERM, Université de Nantes, Université d'Angers, Angers, France.
BMC Mol Biol. 2018 Nov 21;19(1):13. doi: 10.1186/s12867-018-0115-6.
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). Omic analyses were performed using RNA microarray chips and the isotope-coded protein label method (ICPL).
As 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.
In 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.
胶质母细胞瘤（GB）是最常见和侵袭性最强的脑肿瘤。基于基因型的方法以及对转录组或蛋白质组的独立分析，推动了对 GB 基础生物学的理解。联合转录组和蛋白质组谱分析可能会揭示新的生物学见解，并确定用于 GB 治疗的致病机制或治疗靶点。我们报告了 5 例 GB 活检组织（TZ）与相应的瘤周脑区（PBZ）的转录组和蛋白质组数据的比较。使用 RNA 微阵列芯片和同位素编码蛋白质标签法（ICPL）进行了组学分析。
正如在其他癌症中所描述的，我们在 GB 中发现转录组和蛋白质组数据之间的相关性很差。我们仅观察到两个常见的失调 mRNA/蛋白质（神经丝轻链和突触素 1）和 12 个改变的生物学过程；它们与细胞通讯、突触传递和神经系统过程有关。这种较差的相关性可能是产生组学图谱的技术、mRNA 和蛋白质的固有特性以及癌症或 GB 特异性现象的结果。有趣的是，对通过 ICPL 方法鉴定的所有改变蛋白质的开放阅读框上游的转录因子结合位点的分析表明，拓扑异构酶 I 和 p53 结合蛋白 TOPORS 的共同结合位点。在 7/11 TZ 样本中观察到其表达，而在 PBZ 中未观察到。一些研究结果表明，TOPORS 可能作为肿瘤抑制因子发挥作用；在未来的研究中应检查其在胶质瘤发生中的作用。
在这项研究中，我们表明，正如在其他癌症组织中所描述的，GB 样本的转录组和蛋白质组数据之间的相关性较低。我们观察到 NEFL、SYN1 和 12 个生物学过程在转录组和蛋白质组数据中均失调。分析这些过程和这两种蛋白质将非常重要，以确定用于 GB 的新治疗标志物或潜在治疗靶点。
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