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.

Skull-base chordoma (SBC) is a rare, aggressive bone cancer, but its molecular features remain to be characterised. Here, the authors perform proteogenomic analysis of 187 SBC tumours and identify chromosomal instability as a potential prognostic factor and potential therapeutic targets.

Details

Title
Proteogenomic characterization of skull-base chordoma
Author
Zhang, Qilin 1 ; Xu, Ziyan 2 ; Han, Rui 3 ; Wang, Yunzhi 2   VIAFID ORCID Logo  ; Ye, Zhen 3 ; Zhu, Jiajun 2 ; Cai, Yixin 3 ; Zhang, Fan 2 ; Zhao, Jiangyan 2 ; Yao, Boyuan 3 ; Qin, Zhaoyu 2   VIAFID ORCID Logo  ; Qiao, Nidan 3 ; Huang, Ruofan 4 ; Feng, Jinwen 2   VIAFID ORCID Logo  ; Wang, Yongfei 3 ; Rui, Wenting 5 ; He, Fuchu 6   VIAFID ORCID Logo  ; Zhao, Yao 7 ; Ding, Chen 8   VIAFID ORCID Logo 

1  Fudan University, Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Fudan University, National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Massachusetts General Hospital and Harvard Medical School, Neuroendocrine Unit, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
2  Fudan University, Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
3  Fudan University, Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Fudan University, National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
4  Fudan University, National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Fudan University, Department of Oncology, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
5  Fudan University, Department of Radiology, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
6  Fudan University, Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Research Unit of Proteomics Driven Cancer Precision Medicine. Chinese Academy of Medical Sciences, Beijing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839) 
7  Fudan University, Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Fudan University, National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China (GRID:grid.22069.3f) (ISNI:0000 0004 0369 6365); Neurosurgical Institute of Fudan University, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Fudan University, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
8  Fudan University, Center for Cell and Gene Therapy, Clinical Research Center for Cell-based Immunotherapy, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Xinjiang Key Laboratory of Translational Biomedical Engineering, Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China (GRID:grid.512482.8) 
Pages
8338
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-024-52285-7
ProQuest document ID
3110561749
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.