高级别神经胶质瘤的多尺度信号传导和肿瘤进化。
Multi-scale signaling and tumor evolution in high-grade gliomas.
发表日期：2024 Jul 08
作者：
Jingxian Liu, Song Cao, Kathleen J Imbach, Marina A Gritsenko, Tung-Shing M Lih, Jennifer E Kyle, Tomer M Yaron-Barir, Zev A Binder, Yize Li, Ilya Strunilin, Yi-Ting Wang, Chia-Feng Tsai, Weiping Ma, Lijun Chen, Natalie M Clark, Andrew Shinkle, Nataly Naser Al Deen, Wagma Caravan, Andrew Houston, Faria Anjum Simin, Matthew A Wyczalkowski, Liang-Bo Wang, Erik Storrs, Siqi Chen, Ritvik Illindala, Yuping D Li, Reyka G Jayasinghe, Dmitry Rykunov, Sandra L Cottingham, Rosalie K Chu, Karl K Weitz, Ronald J Moore, Tyler Sagendorf, Vladislav A Petyuk, Michael Nestor, Lisa M Bramer, Kelly G Stratton, Athena A Schepmoes, Sneha P Couvillion, Josie Eder, Young-Mo Kim, Yuqian Gao, Thomas L Fillmore, Rui Zhao, Matthew E Monroe, Austin N Southard-Smith, Yang E Li, Rita Jui-Hsien Lu, Jared L Johnson, Maciej Wiznerowicz, Galen Hostetter, Chelsea J Newton, Karen A Ketchum, Ratna R Thangudu, Jill S Barnholtz-Sloan, Pei Wang, David Fenyö, Eunkyung An, Mathangi Thiagarajan, Ana I Robles, D R Mani, Richard D Smith, Eduard Porta-Pardo, Lewis C Cantley, Antonio Iavarone, Feng Chen, Mehdi Mesri, MacLean P Nasrallah, Hui Zhang, Adam C Resnick, Milan G Chheda, Karin D Rodland, Tao Liu, Li Ding, ,
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
尽管胶质母细胞瘤 (GBM) 的基因组异常已被深入研究了十多年，但其 5 年生存率仍然低于 5%。我们寻求通过将蛋白质组学、代谢组学、脂质组学和翻译后修饰 (PTM) 与基因组和转录组学测量相结合来扩展由 IDH 野生型 GBM 和 IDH 突变 4 级星形细胞瘤组成的高级神经胶质瘤的分子景观，以揭示控制肿瘤发展和进化的多尺度调控相互作用。将 14 个蛋白质组学和代谢组学平台应用于 228 个肿瘤（212 个 GBM 和 16 个 4 级 IDH 突变星形细胞瘤），其中包括 28 个复发肿瘤，加上 18 个正常脑样本和 14 个脑转移瘤作为比较，揭示了异质上游变化与常见下游事件的汇合。蛋白质组学和代谢组学水平以及蛋白质-蛋白质相互作用和复发时糖基化位点占用的变化。 PTPN11 上反复发生的基因改变和磷酸化事件在三个维度上映射到重要的调控域，表明 PTPN11 信号在高级别神经胶质瘤中发挥核心作用。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.