PXD053789

PXD053789 is an original dataset announced via ProteomeXchange.

Title	Molecular Profiling Defines Three Subtypes of Synovial Sarcoma
Description	Synovial 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_21:59:43.930.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georgios Mermelekas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-09 03:43:48	ID requested
⏵ 1	2025-05-06 21:59:44	announced

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]

submitter keyword: Synovial Sarcoma

Transcriptomics

Multi-Omic

Molecular Subtypes

Proteomics

Janne Lehtiö
contact affiliation	Department of Oncology and Pathology, Karolinska Institutet, Scilifelab, Stockholm, Sweden
contact email	janne.lehtio@ki.se
lab head
Georgios Mermelekas
contact affiliation	Karolinska Institutet
contact email	georgios.mermelekas@scilifelab.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD053789

PRIDE project URI

• PRIDE
  1. PXD053789
     1. Label: PRIDE project
     2. Name: Molecular Profiling Defines Three Subtypes of Synovial Sarcoma