PXD021838

PXD021838 is an original dataset announced via ProteomeXchange.

Title	Proteomics of muscle microdialysates identifies potential circulating biomarkers in Facioscapulohumeral muscular dystrophy
Description	Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4, a transcription factor normally silenced in skeletal muscle. Detecting DUX4 in skeletal muscle and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for other surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 FSHD patients’ muscles in different disease stages classified by Magnetic Resonance Imaging (MRI) and controls. Serum samples from the same subjects were also analyzed. A total of 1156 proteins were identified in the microdialysates by Data Independent Acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles of interstitial fluids were able to distinguish FSHD patients from controls. Among the upregulated proteins in muscles with active disease, two innate immunity mediators (S100-A8 and A9) and Dermcidin were detected with both proteomic approaches and selectively present in the sera of FSHD patients. Structural muscle proteins were downregulated, consistent with signs of early damage, as well as proteins of the plasminogen pathway. This suggests, together with upstream inhibition in FSHD samples of myogenic factors, defective muscle regeneration and increased fibrosis already in early/active disease. Conclusions: our MRI targeted exploratory approach provided insights on pathophysiological pathways activated in early disease, confirming that inflammatory response has a prominent role, together with impaired muscle regeneration. We also identified three proteins as tissue and possibly circulating prognostic biomarkers in FSHD.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_11:13:14.624.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Victor Corasolla Carregari
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-05 05:50:47	ID requested
⏵ 1	2021-09-09 11:13:15	announced

Corasolla Carregari V, Monforte M, Di Maio G, Pieroni L, Urbani A, Ricci E, Tasca G, Proteomics of Muscle Microdialysates Identifies Potential Circulating Biomarkers in Facioscapulohumeral Muscular Dystrophy. Int J Mol Sci, 22(1):(2020) [pubmed]

submitter keyword: Facioscapulohumeral muscular dystrophy, FSHD, inflammatory response, proteomics, biomarkers

Giorgio Tasca
contact affiliation	Università Cattolica del Sacro Cuore
contact email	giorgiotasca81@gmail.com
lab head
Victor Corasolla Carregari
contact affiliation	Post doctor
contact email	corasolla@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021838
     1. Label: PRIDE project
     2. Name: Proteomics of muscle microdialysates identifies potential circulating biomarkers in Facioscapulohumeral muscular dystrophy