A Time-Based and Intratumoral Proteomic Assessment of a Recurrent Glioblastoma Multiforme.
A Time-Based and Intratumoral Proteomic Assessment of a Recurrent Glioblastoma Multiforme.
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DOI：
10.3389/fonc.2016.00183
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发表时间：
2016
影响因子：
4.7
通讯作者：
Fischer Jde S
中科院分区：
文献类型：
--
作者：
de Aquino PF;Carvalho PC;Nogueira FC;da Fonseca CO;de Souza Silva JC;Carvalho Mda G;Domont GB;Zanchin NI;Fischer Jde S
肿瘤由处于不同转化阶段的细胞组成，具有分子和细胞的异质性。到目前为止，异质性是多形性胶质母细胞瘤（GBM）的特征，这是恶性和侵袭性最强的胶质瘤类型。大多数蛋白质组学研究的目的是比较来自不同患者的肿瘤，但在这里，我们深入探索单个GBM的肿瘤内蛋白质组多样性。为此，我们分析了同一患者GBM深层区域的肿瘤碎片，但从相隔一年的两次手术中获得。我们的分析还包括来自不同解剖区域的GBM碎片。我们的定量蛋白质组学策略采用4-plex iTRAQ肽标记，然后是四步强阳离子色谱分离；然后通过反相纳米色谱法与Orbitrap-Velos质谱联用在线分析各组分。无监督聚类将蛋白质组谱分为四个主要的不同组，并显示大多数变化与肿瘤的解剖区域有关。然而，我们报告了从同一区域的GBM片段中获得的差异丰富的蛋白质，但相隔1年。我们讨论了几个关键蛋白（如S100A9）和与GBM相关的富集途径，如Ras途径，RHO gtpase激活pkn，以及与凋亡相关的途径，仅举几例。据我们所知，这是唯一一份比较同一患者的GBM片段蛋白质组谱的报告。最终，我们的结果推动了科学讨论的前沿，即探索单个组织样本中亚蛋白质组的丰富程度对于更好地了解疾病的重要性，因为每种肿瘤都是独特的。
Tumors consist of cells in different stages of transformation with molecular and cellular heterogeneity. By far, heterogeneity is the hallmark of glioblastoma multiforme (GBM), the most malignant and aggressive type of glioma. Most proteomic studies aim in comparing tumors from different patients, but here we dive into exploring the intratumoral proteome diversity of a single GBM. For this, we profiled tumor fragments from the profound region of the same patient’s GBM but obtained from two surgeries a year’s time apart. Our analysis also included GBM‘s fragments from different anatomical regions. Our quantitative proteomic strategy employed 4-plex iTRAQ peptide labeling followed by a four-step strong cation chromatographic separation; each fraction was then analyzed by reversed-phase nano-chromatography coupled on-line with an Orbitrap-Velos mass spectrometer. Unsupervised clustering grouped the proteomic profiles into four major distinct groups and showed that most changes were related to the tumor’s anatomical region. Nevertheless, we report differentially abundant proteins from GBM’s fragments of the same region but obtained 1 year apart. We discuss several key proteins (e.g., S100A9) and enriched pathways linked with GBM such as the Ras pathway, RHO GTPases activate PKNs, and those related to apoptosis, to name a few. As far as we know, this is the only report that compares GBM fragments proteomic profiles from the same patient. Ultimately, our results fuel the forefront of scientific discussion on the importance in exploring the richness of subproteomes within a single tissue sample for a better understanding of the disease, as each tumor is unique.