PXD070500-1

PXD070500 is an original dataset announced via ProteomeXchange.

Title	The proteome of bilateral macronodular adrenocortical disease (BMAD) shows different profiles correlating with the genetic causes and reveals specific dysregulation of RNA polymerase II and cholesterol biosynthesis enzymes.
Description	Bilateral macronodular adrenocortical disease (BMAD) is currently described as composed of 4 microscopic subtypes (subtype 1 to 4) and 3 molecular groups (ARMC5-altered, KDM1A-altered, and unknown). Little is known about protein heterogeneity and its links with BMAD characteristics. The aim of this work is to study the protein signatures of BMAD and their correlations with microscopy and genetics. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on 24 BMAD: 7 ARMC5, 4 KDM1A, 13 non-KDM1A, non-ARMC5 BMAD and 2 normal adrenal glands as control. Proteomic data were analyzed by principal component analysis followed by non-negative matrix factorization. Unsupervised clustering divided samples into 3 proteomic groups. The first group is composed of ARMC5-altered BMAD and is characterized by accumulation of RNA polymerase II (Pol II) subunits. The second comprises KDM1A-altered patients and subtype 4 BMAD. It is characterized by accumulation of cholesterol biosynthesis enzymes (such as FDFT1). The final group has no specific signature detected and is composed of subtypes 1 and 3 BMAD. Our study is the first to explore BMAD proteome using LC-MS/MS. The 3 proteomic groups mostly overlap the 4 microscopic and 3 molecular groups of BMAD. Accumulation of Pol II subunits induced by ARMC5 inactivation is probably plays a role in the pathogenesis of those BMAD. KDM1A-altered and subtype 4 BMAD showed an accumulation of proteins involved in lipid metabolism that could contribute to hypercortisolism. These results reveal specific protein patterns pointing to various cellular processes opening new perspective to understand BMAD pathophysiology.
HostingRepository	PRIDE
AnnounceDate	2025-12-18
AnnouncementXML	Submission_2025-12-17_22:55:30.149.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guilhem Clary
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-09 06:06:43	ID requested
⏵ 1	2025-12-17 22:55:30	announced

Dataset with its publication pending

submitter keyword: Bilateral macronodular adrenocortical disease, KDM1A, ARMC5

Jérôme Bertherat
contact affiliation	1. Paris-Cité university, Cochin institute CNRS UMR8104, Inserm U1016, 24 rue du faubourg Saint Jacques 75014 Paris, France 2. Department of Endocrinology and National Reference Center for Rare Adrenal Disorders, Cochin hospital, Assistance Publique Hôpitaux de Paris, 24 rue du faubourg Saint Jacques 75014 Paris, France
contact email	jerome.bertherat@aphp.fr
lab head
Guilhem Clary
contact affiliation	Istitut Cochin
contact email	guilhem.clary@inserm.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD070500
     1. Label: PRIDE project
     2. Name: The proteome of bilateral macronodular adrenocortical disease (BMAD) shows different profiles correlating with the genetic causes and reveals specific dysregulation of RNA polymerase II and cholesterol biosynthesis enzymes.