Proteomic profiling of gliomas unveils immune and metabolism-driven subtypes with implications for anti-nucleotide metabolism therapy

被引：8

作者：

Zhang, Jinsen ^{[1
,2
,3
,4
,5
]}

Sun, Rui ^{[6
,7
,8
]}

Lyu, Yingying ^{[1
,2
,3
,4
,5
]}

Liu, Chaxian ^{[1
,2
,3
,4
,5
]}

Liu, Ying ^{[9
]}

Feng, Yuan ^{[1
,2
,3
,4
,5
]}

Fu, Minjie ^{[1
,2
,3
,4
,5
]}

Wong, Peter Jih Cheng ^{[1
,2
,3
,4
,5
]}

Du, Zunguo ^{[10
]}

Qiu, Tianming ^{[1
,2
,3
,4
,5
]}

Zhang, Yi ^{[1
,2
,3
,4
,5
]}

Zhuang, Dongxiao ^{[1
,2
,3
,4
,5
]}

Qin, Zhiyong ^{[1
,2
,3
,4
,5
]}

Yao, Yu ^{[1
,2
,3
,4
,5
]}

Zhu, Wei ^{[1
,2
,3
,4
,5
]}

Guo, Tiannan ^{[6
,7
,8
]}

Hua, Wei ^{[1
,2
,3
,4
,5
]}

Yang, Hui ^{[1
,2
,3
,4
,5
,11
,12
]}

Mao, Ying ^{[1
,2
,3
,4
,5
]}

机构：

[1] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai, Peoples R China

[2] Natl Ctr Neurol Disorders, Shanghai, Peoples R China

[3] Shanghai Key Lab Brain Funct & Restorat & Neural, Shanghai, Peoples R China

[4] Fudan Univ, Neurosurg Inst, Shanghai, Peoples R China

[5] Shanghai Clin Med Ctr Neurosurg, Shanghai, Peoples R China

[6] Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, State Key Lab Med Prote, Hangzhou, Zhejiang, Peoples R China

[7] Westlake Ctr Intelligent Prote, Westlake Lab Life Sci & Biomed, Hangzhou, Zhejiang, Peoples R China

[8] Westlake Univ, Res Ctr Ind Future, Sch Life Sci, Hangzhou, Zhejiang, Peoples R China

[9] Fudan Univ, Shanghai Med Coll, Dept Pathol, Shanghai, Peoples R China

[10] Fudan Univ, Huashan Hosp, Dept Pathol, Shanghai, Peoples R China

[11] Fudan Univ, Inst Translat Brain Res, Shanghai Med Coll, State Key Lab Med Neurobiol, Shanghai, Peoples R China

[12] Fudan Univ, Inst Translat Brain Res, Shanghai Med Coll, MOE Frontiers Ctr Brain Sci, Shanghai, Peoples R China

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

CENTRAL-NERVOUS-SYSTEM; THYMIDINE PHOSPHORYLASE; PROTEOGENOMIC CHARACTERIZATION; MUTATIONS; CANCER; CELLS; CHEMORADIOTHERAPY; CLASSIFICATION; HALLMARKS; GROWTH;

D O I：

10.1038/s41467-024-54352-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gliomas exhibit high heterogeneity and poor prognosis. Despite substantial progress has been made at the genomic and transcriptomic levels, comprehensive proteomic characterization and its implications remain largely unexplored. In this study, we perform proteomic profiling of gliomas using 343 formalin-fixed and paraffin-embedded tumor samples and 53 normal-appearing brain samples from 188 patients, integrating these data with genomic panel information and clinical outcomes. The proteomic analysis uncovers two distinct subgroups: Subgroup 1, the metabolic neural subgroup, enriched in metabolic enzymes and neurotransmitter receptor proteins, and Subgroup 2, the immune subgroup, marked by upregulation of immune and inflammatory proteins. These proteomic subgroups show significant differences in prognosis, tumorigenesis, microenvironment dysregulation, and potential therapeutics, highlighting the critical roles of metabolic and immune processes in glioma biology and patient outcomes. Through a detailed investigation of metabolic pathways guided by our proteomic findings, dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP) emerge as potential prognostic biomarkers linked to the reprogramming of nucleotide metabolism. Functional validation in patient-derived glioma stem cells and animal models highlights nucleotide metabolism as a promising therapy target for gliomas. This integrated multi-omics analysis introduces a proteomic classification for gliomas and identifies DPYD and TYMP as key metabolic biomarkers, offering insights into glioma pathogenesis and potential treatment strategies. Comprehensive molecular characterisations could shed light on the high heterogeneity and poor prognosis of gliomas. Here, the authors perform proteomic profiling of 188 glioma patients, revealing immune and metabolic neuron-related subgroups as well as metabolic biomarkers linked to prognosis.

引用

页数：15

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