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Proteomic profiling of soft tissue sarcomas with SWATH mass spectrometry
- Source :
- Journal of Proteomics
- Publication Year :
- 2020
- Publisher :
- Cold Spring Harbor Laboratory, 2020.
-
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.<br />Graphical abstract Unlabelled Image<br />Highlights • Proteomic analysis of FFPE specimens from four soft tissue sarcoma histological subtypes was performed by SWATH MS. • Subtype-specific biological pathways and protein-protein interaction networks were identified. • A panel of proteins associated with sarcoma patient survival outcome was defined. • A subset of proteins identified by SWATH MS was validated by orthogonal immunohistochemical analysis.
- Subjects :
- Proteomics
Leiomyosarcoma
0301 basic medicine
Pathology
medicine.medical_specialty
SWATH MS
Biophysics
Biology
FFPE
Biochemistry
Article
Undifferentiated Pleomorphic Sarcoma
03 medical and health sciences
medicine
Humans
Epigenomics
Soft tissue sarcoma
Mass spectrometry
030102 biochemistry & molecular biology
Proteomic Profiling
Gene Expression Profiling
Soft tissue
Sarcoma
Smooth muscle contraction
medicine.disease
Synovial sarcoma
030104 developmental biology
RNA splicing
Biomarkers
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Journal of Proteomics
- Accession number :
- edsair.doi.dedup.....7f68f98d02ead8e73cecd9c0ed84edeb