The proteomic landscape of soft tissue sarcomas.
Burns, Jessica Wilding, Christopher P Krasny, Lukas Zhu, Xixuan Chadha, Madhumeeta Tam, Yuen Bun Ps, Hari Mahalingam, Aswanth H Lee, Alexander T J Arthur, Amani
Burns, Jessica
Wilding, Christopher P
Krasny, Lukas
Zhu, Xixuan
Chadha, Madhumeeta
Tam, Yuen Bun
Ps, Hari
Mahalingam, Aswanth H
Lee, Alexander T J
Arthur, Amani
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2023-06-29
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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.
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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. The proteomic landscape of soft tissue sarcomas. Nat Commun. 2023 Jun 29;14(1):3834. doi: 10.1038/s41467-023-39486-2. PMID: 37386008; PMCID: PMC10310735.
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