Nature Communications (Jun 2023)
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,
- Paul H. Huang
Affiliations
- Jessica Burns
- Division of Molecular Pathology, The Institute of Cancer Research
- Christopher P. Wilding
- Division of Molecular Pathology, The Institute of Cancer Research
- Lukas Krasny
- Division of Molecular Pathology, The Institute of Cancer Research
- Xixuan Zhu
- Division of Clinical Studies, The Institute of Cancer Research
- Madhumeeta Chadha
- Division of Molecular Pathology, The Institute of Cancer Research
- Yuen Bun Tam
- Division of Molecular Pathology, The Institute of Cancer Research
- Hari PS
- Division of Molecular Pathology, The Institute of Cancer Research
- Aswanth H. Mahalingam
- Division of Molecular Pathology, The Institute of Cancer Research
- Alexander T. J. Lee
- Division of Molecular Pathology, The Institute of Cancer Research
- Amani Arthur
- Division of Molecular Pathology, The Institute of Cancer Research
- Nafia Guljar
- Division of Molecular Pathology, The Institute of Cancer Research
- Emma Perkins
- Division of Molecular Pathology, The Institute of Cancer Research
- Valeriya Pankova
- Division of Molecular Pathology, The Institute of Cancer Research
- Andrew Jenks
- Division of Molecular Pathology, The Institute of Cancer Research
- Vanessa Djabatey
- Division of Molecular Pathology, The Institute of Cancer Research
- Cornelia Szecsei
- Division of Molecular Pathology, The Institute of Cancer Research
- Frank McCarthy
- Division of Molecular Pathology, The Institute of Cancer Research
- Chanthirika Ragulan
- Division of Molecular Pathology, The Institute of Cancer Research
- Martina Milighetti
- Division of Molecular Pathology, The Institute of Cancer Research
- Theodoros I. Roumeliotis
- Division of Cancer Biology, The Institute of Cancer Research
- Stephen Crosier
- Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University
- Martina Finetti
- Leeds Institute of Medical Research at St James’s, St James’s University Hospital
- Jyoti S. Choudhary
- Division of Cancer Biology, The Institute of Cancer Research
- Ian Judson
- The Royal Marsden NHS Foundation Trust
- Cyril Fisher
- University Hospitals Birmingham NHS Foundation Trust
- Eugene F. Schuster
- Ralph Lauren Centre for Breast Cancer Research, The Royal Marsden NHS Foundation Trust
- Anguraj Sadanandam
- Division of Molecular Pathology, The Institute of Cancer Research
- Tom W. Chen
- Department of Oncology, National Taiwan University Hospital
- Daniel Williamson
- Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University
- Khin Thway
- Division of Molecular Pathology, The Institute of Cancer Research
- Robin L. Jones
- Division of Clinical Studies, The Institute of Cancer Research
- Maggie C. U. Cheang
- Division of Clinical Studies, The Institute of Cancer Research
- Paul H. Huang
- Division of Molecular Pathology, The Institute of Cancer Research
- DOI
- https://doi.org/10.1038/s41467-023-39486-2
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.
