Proteogenomics of diffuse gliomas reveal molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms

Yunzhi Wang, Rongkui Luo, Xuan Zhang, Hang Xiang, Bing Yang, Jinwen Feng, Mengjie Deng, Peng Ran, Akesu Sujie, Fan Zhang, Jiajun Zhu, Subei Tan, Tao Xie, Pin Chen, Zixiang Yu, Yan Li, Dongxian Jiang, Xiaobiao Zhang (), Jian-Yuan Zhao (), Yingyong Hou () and Chen Ding ()
Additional contact information
Yunzhi Wang: Fudan University
Rongkui Luo: Fudan University
Xuan Zhang: Fudan University Shanghai Cancer Center
Hang Xiang: Fudan University
Bing Yang: Fudan University
Jinwen Feng: Fudan University
Mengjie Deng: Fudan University
Peng Ran: Fudan University
Akesu Sujie: Fudan University
Fan Zhang: Fudan University
Jiajun Zhu: Fudan University
Subei Tan: Fudan University
Tao Xie: Fudan University
Pin Chen: Fudan University
Zixiang Yu: Fudan University
Yan Li: Fudan University
Dongxian Jiang: Fudan University
Xiaobiao Zhang: Fudan University
Jian-Yuan Zhao: Shanghai Jiao Tong University School of Medicine
Yingyong Hou: Fudan University
Chen Ding: Fudan University

Nature Communications, 2023, vol. 14, issue 1, 1-32

Abstract: Abstract Diffuse gliomas are devastating brain tumors. Here, we perform a proteogenomic profiling of 213 retrospectively collected glioma tumors. Proteogenomic analysis reveals the downstream biological events leading by EGFR-, IDH1-, TP53-mutations. The comparative analysis illustrates the distinctive features of GBMs and LGGs, indicating CDK2 inhibitor might serve as a promising drug target for GBMs. Further proteogenomic integrative analysis combined with functional experiments highlight the cis-effect of EGFR alterations might lead to glioma tumor cell proliferation through ERK5 medicates nucleotide synthesis process. Proteome-based stratification of gliomas defines 3 proteomic subgroups (S-Ne, S-Pf, S-Im), which could serve as a complement to WHO subtypes, and would provide the essential framework for the utilization of specific targeted therapies for particular glioma subtypes. Immune clustering identifies three immune subtypes with distinctive immune cell types. Further analysis reveals higher EGFR alteration frequencies accounts for elevation of immune check point protein: PD-L1 and CD70 in T-cell infiltrated tumors.

Date: 2023
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DOI: 10.1038/s41467-023-36005-1

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