The proteomic landscape of soft tissue sarcomas.
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Date
2023-06-29ICR Author
Author
Burns, J
Wilding, CP
Krasny, L
Zhu, X
Chadha, M
Tam, YB
Ps, H
Mahalingam, AH
Lee, ATJ
Arthur, A
Guljar, N
Perkins, E
Pankova, V
Jenks, A
Djabatey, V
Szecsei, C
McCarthy, F
Ragulan, C
Milighetti, M
Roumeliotis, TI
Crosier, S
Finetti, M
Choudhary, JS
Judson, I
Fisher, C
Schuster, EF
Sadanandam, A
Chen, TW
Williamson, D
Thway, K
Jones, RL
Cheang, MCU
Huang, PH
Type
Journal Article
Metadata
Show full item recordAbstract
Soft tissue sarcomas (STS) are rare and diverse mesenchymal cancers with limited treatment options. Here we undertake comprehensive proteomic profiling of tumour specimens from 321 STS patients representing 11 histological subtypes. Within leiomyosarcomas, we identify three proteomic subtypes with distinct myogenesis and immune features, anatomical site distribution and survival outcomes. Characterisation of undifferentiated pleomorphic sarcomas and dedifferentiated liposarcomas with low infiltrating CD3 + T-lymphocyte levels nominates the complement cascade as a candidate immunotherapeutic target. Comparative analysis of proteomic and transcriptomic profiles highlights the proteomic-specific features for optimal risk stratification in angiosarcomas. Finally, we define functional signatures termed Sarcoma Proteomic Modules which transcend histological subtype classification and show that a vesicle transport protein signature is an independent prognostic factor for distant metastasis. Our study highlights the utility of proteomics for identifying molecular subgroups with implications for risk stratification and therapy selection and provides a rich resource for future sarcoma research.
Collections
Research team
Clin Trials & Stats Unit
Functional Proteomics
Prote & Metabolomics Fac
Endocrine Therapy Resist
Systems - Precision Med
Mol and Systems Oncology
Language
eng
Date accepted
2023-06-15
License start date
2023-06-29
Citation
Nature Communications, 2023, 14 (1), pp. 3834 -
Publisher
NATURE PORTFOLIO