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

doi:10.1038/s41467-024-52285-7

Proteogenomic characterization of skull-base chordoma

Nat Commun. 2024 Sep 27;15(1):8338. doi: 10.1038/s41467-024-52285-7.

Authors

Qilin Zhang^#^{1

2

3}, Ziyan Xu^#¹, Rui Han^#^{1

2}, Yunzhi Wang^#¹, Zhen Ye^#^{1

2}, Jiajun Zhu^#¹, Yixin Cai^#^{1

2}, Fan Zhang^#¹, Jiangyan Zhao^#¹, Boyuan Yao^{1

2}, Zhaoyu Qin¹, Nidan Qiao^{1

2}, Ruofan Huang^{2

4}, Jinwen Feng¹, Yongfei Wang^{1

2}, Wenting Rui⁵, Fuchu He^{6

7}, Yao Zhao^{8

9

10

11

12

13}, Chen Ding^{14

15}

Affiliations

¹ 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, Shanghai, 200433, China.
² National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
³ Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Oncology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
⁵ Department of Radiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ 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, Shanghai, 200433, China. hefc@nic.bmi.ac.cn.
⁷ Research Unit of Proteomics Driven Cancer Precision Medicine. Chinese Academy of Medical Sciences, Beijing, 102206, China. hefc@nic.bmi.ac.cn.
⁸ 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, Shanghai, 200433, China. zhaoyaohs@vip.sina.com.
⁹ National Center for Neurological Disorders, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. zhaoyaohs@vip.sina.com.
¹⁰ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. zhaoyaohs@vip.sina.com.
¹¹ Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, 200040, China. zhaoyaohs@vip.sina.com.
¹² Neurosurgical Institute of Fudan University, Shanghai, 200040, China. zhaoyaohs@vip.sina.com.
¹³ National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China. zhaoyaohs@vip.sina.com.
¹⁴ 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, Shanghai, 200433, China. chend@fudan.edu.cn.
¹⁵ Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, 830000, China. chend@fudan.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Chordoma* / genetics
Chordoma* / metabolism
Chordoma* / pathology
Chromosomal Instability*
Chromosomes, Human, Pair 1 / genetics
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Prognosis
Proteogenomics* / methods
Proteomics
Skull Base Neoplasms* / genetics
Skull Base Neoplasms* / metabolism
Skull Base Neoplasms* / pathology