Nature Communications (Sep 2024)
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,
- Chen Ding
Affiliations
- Qilin Zhang
- 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, Fudan University
- Ziyan Xu
- 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, Fudan University
- Rui Han
- 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, Fudan University
- Yunzhi Wang
- 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, Fudan University
- Zhen Ye
- 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, Fudan University
- Jiajun Zhu
- 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, Fudan University
- Yixin Cai
- 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, Fudan University
- Fan Zhang
- 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, Fudan University
- Jiangyan Zhao
- 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, Fudan University
- Boyuan Yao
- 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, Fudan University
- Zhaoyu Qin
- 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, Fudan University
- Nidan Qiao
- 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, Fudan University
- Ruofan Huang
- National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University
- Jinwen Feng
- 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, Fudan University
- Yongfei Wang
- 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, Fudan University
- Wenting Rui
- Department of Radiology, Huashan Hospital, Shanghai Medical College, Fudan University
- Fuchu He
- 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, Fudan University
- Yao Zhao
- 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, Fudan University
- Chen Ding
- 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, Fudan University
- DOI
- https://doi.org/10.1038/s41467-024-52285-7
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
