Proteomic profiling of soft tissue sarcomas with SWATH mass spectrometry.

Thumbnail Image

Files

1-s2.0-S1874391921001354-main.pdf (9.5 MB)

Embargo End Date

ICR Authors

Krasny, Lukas
 Wilding, Christopher
 Arthur, Amani
 Judson, Ian
 Cheang, Chon
 Jones, Robin
 Huang, Paul

Authors

Milighetti, M
Krasny, L
Lee, ATJ
Morani, G
Szecsei, C
Chen, Y
Guljar, N
McCarthy, F
Wilding, CP
Arthur, A
Fisher, C
Judson, I
Thway, K
Cheang, MCU
Jones, RL
Huang, PH

Document Type

Journal Article

Date

2021-06-15

Date Accepted

2021-04-14

Abstract

Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers. While large-scale genomic and epigenomic profiling of STS have been undertaken, proteomic analysis has thus far been limited. Here we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n = 36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma). We quantified 2951 proteins across all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma. We further identified a subgroup of STS cases that have a distinct expression profile in a panel of proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.

Citation

Journal of proteomics, 2021, 241 pp. 104236 - ?

DOI

10.1016/j.jprot.2021.104236

URI

https://repository.icr.ac.uk/handle/internal/4667

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

ELSEVIER

ISSN

1874-3919

eISSN

1876-7737

Collections

Clinical Studies
Cancer Biology

Research Team

Genomic Analysis – Clinical Trials
Sarcoma Clinical Trials (R Jones)
Molecular and Systems Oncology
Genomic Analysis – Clinical Trials
Sarcoma Clinical Trials (R Jones)
Molecular and Systems Oncology

Notes