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PXD053789

PXD053789 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMolecular Profiling Defines Three Subtypes of Synovial Sarcoma
DescriptionSynovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex (BRG1/BRM-associated factor complex), which leads to widespread alterations in gene expression that drive tumor development and progression. However, there are no comprehensive studies that integrate multi-omics approaches to fully understand the heterogeneity and molecular subtypes of SS. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single-cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular-stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our multi-omics analysis revealed biological and genetic variability between these subtypes, including key transcriptome patterns and secondary genomic events such as copy number alterations, could be associated with long-term outcomes. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-06_21:59:43.930.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGeorgios Mermelekas
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-09 03:43:48ID requested
12025-05-06 21:59:44announced
Publication List
10.1002/advs.202404510;
Chen Y, Su Y, Cao X, Siavelis I, Leo IR, Zeng J, Tsagkozis P, Hesla AC, Papakonstantinou A, Liu X, Huang WK, Zhao B, Haglund C, Ehnman M, Johansson H, Lin Y, Lehti, ö J, Zhang Y, Larsson O, Li X, de Flon FH, Molecular Profiling Defines Three Subtypes of Synovial Sarcoma. Adv Sci (Weinh), 11(41):e2404510(2024) [pubmed]
Keyword List
submitter keyword: Synovial Sarcoma
Transcriptomics
Multi-Omic
Molecular Subtypes
Proteomics
Contact List
Janne Lehtiö
contact affiliationDepartment of Oncology and Pathology, Karolinska Institutet, Scilifelab, Stockholm, Sweden
contact emailjanne.lehtio@ki.se
lab head
Georgios Mermelekas
contact affiliationKarolinska Institutet
contact emailgeorgios.mermelekas@scilifelab.se
dataset submitter
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Dataset FTP location
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