PXD069421

PXD069421 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling identifies key proteins, pathways and molecular subtypes regulating chemo-radio-sensitivity and relapse in rhabdomyosarcoma
Description	Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, exhibits marked clinical heterogeneity driven by poorly understood molecular mechanisms. Identifying the molecular characteristics of different RMS subtypes and the molecular pathways influencing RMS treatment response and recurrence is an urgent clinical need. Here, we perform deep proteomic profiling of 19 RMS tumors (8 alveolar [ARMS], 11 embryonal [ERMS]) and matched normal tissues, integrating bioinformatics with functional validation to delineate subtype-specific pathways, therapy resistance drivers, and actionable targets. ARMS tumors are characterized by ubiquitination pathway activation (UBE2R2, UBE2J2), while ERMS exhibits spliceosome dysregulation. Chemo- and radio-resistant tumors both show significant enrichment in ribosome pathway. Relapsed cases show phosphonate and phosphinate metabolism pathway enrichment, suggesting metabolism reliance. Unsupervised clustering reveals ribosome- and glycolysis-driven subtypes with distinct metabolic dependencies. Functional studies implicate MED18—a core component of the Mediator complex—in mediating therapy resistance possibly via promoting DNA damage repair. Our study establishes proteomics as a tool to decode RMS heterogeneity, proposing subtype-tailored strategies targeting ubiquitination, splicing, and metabolism.
HostingRepository	iProX
AnnounceDate	2025-10-14
AnnouncementXML	Submission_2026-01-04_00:15:00.990.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhiyuan Zhou
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-13 23:53:17	ID requested
⏵ 1	2026-01-04 00:15:01	announced

Dataset with its publication pending

submitter keyword: rhabdomyosarcoma, proteomics, chemo-sensitivity, radio-sensitivity, relapse

Lu Wen
contact affiliation	Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
contact email	wenlu2808@126.com
lab head
Zhiyuan Zhou
contact affiliation	Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
contact email	zhouzhiyuan@hust.edu.cn
dataset submitter

iProX dataset URI