美国华盛顿大学Li Ding、西北太平洋国家实验室Tao Liu和Karin D. Rodland研究组合作揭示了人胶质母细胞瘤（GBM）的蛋白质组学和代谢组学特征。2021年4月12日，国际学术期刊《癌细胞》发表了这一成果。

研究人员发现关键基因的磷酸化（例如，PTPN11和PLCG1的磷酸化）是介导致癌途径激活的潜在开关，以及EGFR、TP53和RB1突变肿瘤的潜在靶标。使用大量组学方法，研究发现了含有不同类型免疫细胞的免疫亚型，并通过snRNA-seq进行了验证，并将其与特异性表达和组蛋白乙酰化相关联。

经典的GBM和免疫受损GBM中的组蛋白H2B乙酰化主要受BRD、CREBBP和EP300的调控。整合代谢组学和蛋白质组学数据可确定IDH突变型肿瘤中不同亚型的特定脂质分布和显著的整体代谢变化。这项工作揭示的生物学关系可能有助于GBM患者分型和获得更有效的治疗。

据介绍，胶质母细胞瘤是最具侵略性的神经系统癌症。了解其发病的分子机制对改善诊断和治疗至关重要。对99种未经治疗GBM基因组学、蛋白质组学、翻译后修饰和代谢组学数据的综合分析为了解GBM生物学提供了见解。

附：英文原文

Title: Proteogenomic and metabolomic characterization of human glioblastoma

Author: Liang-Bo Wang, Alla Karpova, Marina A. Gritsenko, Jennifer E. Kyle, Song Cao, Yize Li, Dmitry Rykunov, Antonio Colaprico, Joseph H. Rothstein, Runyu Hong, Vasileios Stathias, MacIntosh Cornwell, Francesca Petralia, Yige Wu, Boris Reva, Karsten Krug, Pietro Pugliese, Emily Kawaler, Lindsey K. Olsen, Wen-Wei Liang, Xiaoyu Song, Yongchao Dou, Michael C. Wendl, Wagma Caravan, Wenke Liu, Daniel Cui Zhou, Jiayi Ji, Chia-Feng Tsai, Vladislav A. Petyuk, Jamie Moon, Weiping Ma, Rosalie K. Chu, Karl K. Weitz, Ronald J. Moore, Matthew E. Monroe, Rui Zhao, Xiaolu Yang, Seungyeul Yoo, Azra Krek, Alexis Demopoulos, Houxiang Zhu, Matthew A. Wyczalkowski, Joshua F. McMichael, Brittany L. Henderson, Caleb M. Lindgren, Hannah Boekweg, Shuangjia Lu, Jessika Baral, Lijun Yao, Kelly G. Stratton, Lisa M. Bramer, Erika Zink, Sneha P. Couvillion, Kent J. Bloodsworth, Shankha Satpathy, Weiva Sieh, Simina M. Boca, Stephan Schürer

Issue&Volume: 2021/04/12

Abstract: Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.

DOI: 10.1016/j.ccell.2021.01.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00050-7