Proteogenomic characterization of skull-base chordoma
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.
Authors
- Rui Han (ORCID: https://orcid.org/0000-0001-8856-3681)
- Nidan Qiao (ORCID: https://orcid.org/0000-0001-5478-3555)
- Jinwen Feng (ORCID: https://orcid.org/0000-0003-1683-4280)
- Wenting Rui (ORCID: https://orcid.org/0000-0002-2241-0639)
- Zhaoyu Qin (ORCID: https://orcid.org/0000-0003-4437-0268)
- Yao Zhao (ORCID: https://orcid.org/0000-0002-2734-7907)
- Boyuan Yao (ORCID: https://orcid.org/0000-0001-6448-2588)
- Fan Zhang (ORCID: https://orcid.org/0000-0002-6758-2856)
- Chen Ding (ORCID: https://orcid.org/0000-0001-8673-3464)
- Qilin Zhang (ORCID: https://orcid.org/0000-0002-0122-3201)
- Yongfei Wang (ORCID: https://orcid.org/0000-0002-8926-252X)
- Yixin Cai
- Yunzhi Wang (ORCID: https://orcid.org/0000-0002-1086-8896)
- Jiajun Zhu (ORCID: https://orcid.org/0000-0001-6488-6419)
- Jiangyan Zhao (ORCID: https://orcid.org/0000-0001-6891-5037)
- Fuchu He (ORCID: https://orcid.org/0000-0002-1094-4019)
- Zhen Ye (ORCID: https://orcid.org/0009-0000-8766-8262)
- Ziyan Xu
- Ruofan Huang
Institutions
- Allen Institute for Brain Science (US)
- Harvard University (US)
- Xinjiang Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fudan University (CN)
- Massachusetts General Hospital (US)
- Tumor Hospital of Xinjiang Medical University (CN)
- Huashan Hospital (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1038/s41467-024-52285-7
- Citations
- 9
- Primary Topic
- Bone Tumor Diagnosis and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.23
Funders
- Cancer Research Institute
- Chordoma Foundation
- National Natural Science Foundation of China
- Fudan University
- National High-tech Research and Development Program
- National Key Research and Development Program of China
- Program of Shanghai Academic Research Leader
- National Science Fund for Distinguished Young Scholars
- National Program for Support of Top-notch Young Professionals