Proteogenomic characterization of skull-base chordoma

Qilin Zhang, Ziyan Xu, Rui Han, Yunzhi Wang, Zhen Ye, Jiajun Zhu, Yixin Cai, Fan Zhang, Jiangyan Zhao, Boyuan Yao, Zhaoyu Qin, Nidan Qiao, Ruofan Huang, Jinwen Feng, Yongfei Wang, Wenting Rui, Fuchu He (), Yao Zhao () and Chen Ding ()
Additional contact information
Qilin Zhang: Fudan University
Ziyan Xu: Fudan University
Rui Han: Fudan University
Yunzhi Wang: Fudan University
Zhen Ye: Fudan University
Jiajun Zhu: Fudan University
Yixin Cai: Fudan University
Fan Zhang: Fudan University
Jiangyan Zhao: Fudan University
Boyuan Yao: Fudan University
Zhaoyu Qin: Fudan University
Nidan Qiao: Fudan University
Ruofan Huang: Fudan University
Jinwen Feng: Fudan University
Yongfei Wang: Fudan University
Wenting Rui: Fudan University
Fuchu He: Fudan University
Yao Zhao: Fudan University
Chen Ding: Fudan University

Nature Communications, 2024, vol. 15, issue 1, 1-32

Abstract: Abstract Skull-base chordoma is a rare, aggressive bone cancer with a high recurrence rate. Despite advances in genomic studies, its molecular characteristics and effective therapies remain unknown. Here, we conduct integrative genomics, transcriptomics, proteomics, and phosphoproteomics analyses of 187 skull-base chordoma tumors. In our study, chromosome instability is identified as a prognostic predictor and potential therapeutic target. Multi-omics data reveals downstream effects of chromosome instability, with RPRD1B as a putative target for radiotherapy-resistant patients. Chromosome 1q gain, associated with chromosome instability and upregulated mitochondrial functions, lead to poorer clinical outcomes. Immune subtyping identify an immune cold subtype linked to chromosome 9p/10q loss and immune evasion. Proteomics-based classification reveals subtypes (P-II and P-III) with high chromosome instability and immune cold features, with P-II tumors showing increased invasiveness. These findings, confirmed in 17 paired samples, provide insights into the biology and treatment of skull-base chordoma.

Date: 2024
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DOI: 10.1038/s41467-024-52285-7

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