The proteomic landscape of soft tissue sarcomas

Jessica Burns, Christopher P. Wilding, Lukas Krasny, Xixuan Zhu, Madhumeeta Chadha, Yuen Bun Tam, Hari Ps, Aswanth H. Mahalingam, Alexander T. J. Lee, Amani Arthur, Nafia Guljar, Emma Perkins, Valeriya Pankova, Andrew Jenks, Vanessa Djabatey, Cornelia Szecsei, Frank McCarthy, Chanthirika Ragulan, Martina Milighetti, Theodoros I. Roumeliotis, Stephen Crosier, Martina Finetti, Jyoti S. Choudhary, Ian Judson, Cyril Fisher, Eugene F. Schuster, Anguraj Sadanandam, Tom W. Chen, Daniel Williamson, Khin Thway, Robin L. Jones, Maggie C. U. Cheang and Paul H. Huang ()
Additional contact information
Jessica Burns: The Institute of Cancer Research
Christopher P. Wilding: The Institute of Cancer Research
Lukas Krasny: The Institute of Cancer Research
Xixuan Zhu: The Institute of Cancer Research
Madhumeeta Chadha: The Institute of Cancer Research
Yuen Bun Tam: The Institute of Cancer Research
Hari Ps: The Institute of Cancer Research
Aswanth H. Mahalingam: The Institute of Cancer Research
Alexander T. J. Lee: The Institute of Cancer Research
Amani Arthur: The Institute of Cancer Research
Nafia Guljar: The Institute of Cancer Research
Emma Perkins: The Institute of Cancer Research
Valeriya Pankova: The Institute of Cancer Research
Andrew Jenks: The Institute of Cancer Research
Vanessa Djabatey: The Institute of Cancer Research
Cornelia Szecsei: The Institute of Cancer Research
Frank McCarthy: The Institute of Cancer Research
Chanthirika Ragulan: The Institute of Cancer Research
Martina Milighetti: The Institute of Cancer Research
Theodoros I. Roumeliotis: The Institute of Cancer Research
Stephen Crosier: Newcastle University
Martina Finetti: St James’s University Hospital
Jyoti S. Choudhary: The Institute of Cancer Research
Ian Judson: The Royal Marsden NHS Foundation Trust
Cyril Fisher: University Hospitals Birmingham NHS Foundation Trust
Eugene F. Schuster: The Royal Marsden NHS Foundation Trust
Anguraj Sadanandam: The Institute of Cancer Research
Tom W. Chen: National Taiwan University Hospital
Daniel Williamson: Newcastle University
Khin Thway: The Institute of Cancer Research
Robin L. Jones: The Institute of Cancer Research
Maggie C. U. Cheang: The Institute of Cancer Research
Paul H. Huang: The Institute of Cancer Research

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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Citations: View citations in EconPapers (3)

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DOI: 10.1038/s41467-023-39486-2

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