PXD031323

PXD031323 is an original dataset announced via ProteomeXchange.

Title	Characterization of tumor heterogeneity in beta-catenin mutated hepatocellular adenomas
Description	Hepatocellular adenomas (HCA) are rare benign tumours of the liver which have been extensively classified at the clinico-pathological, genetic and proteomic levels. The b-HCA subtype has several types of mutations in the ß-catenin gene (CTNNB1) with very different clinical phenotypes and risks. Recently, we revealed a glutamine synthetase (GS) positive rim in b-HCA exon 3 S45 and b-HCA exon 7/8, indicating protein expression heterogeneity into b-HCA in comparison with the rest of the tumor. A difference in vascularization had been associated with this rim revealed by a diffuse CD34 labeling only at the center of the tumor and not in the rim. In this study, we sought to characterize this tumor heterogeneity in a tumor considered monoclonal. We used laser microdissection to analyze the rim (R) at the molecular level. We cut 1mm² areas of GS+/CD34- rim on serial cuts and we analyzed in parallel, the mutation status of CTNNB1 and the levels of protein expression by mass spectrometry. Comparison of the proteomic profiles of the rim versus the tumor center (T) revealed a sufficiently large protein expression differential to distinguish them by principal component analysis. Forty proteins were significantly differentially expressed between R and T, including a large majority of amino acid and lipid metabolism proteins whose deregulations were comparable to a perivenous expression profile in a normal hepatocyte context. Our results suggest that protein expression in the rim seems not to be dependent on the mutational status of CTNNB1 but rather on the influence of venous drainage. Thanks to laser microdissection coupled with proteomic analysis on fixed tissue, we were able to analyze this tumor heterogeneity and provide elements of biological interpretation.
HostingRepository	PRIDE
AnnounceDate	2024-01-16
AnnouncementXML	Submission_2024-01-16_07:54:05.682.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dupuy Jean-William
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-30 10:48:59	ID requested
1	2023-05-02 03:39:28	announced
2	2023-11-14 08:45:22	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-01-16 07:54:06	announced	2024-01-16: Updated project metadata.

Dourthe C, Julien C, Di Tommaso S, Dupuy JW, Dugot-Senant N, Brochard A, Le Bail B, Blanc JF, Chiche L, Balabaud C, Bioulac-Sage P, Saltel F, Raymond AA, Proteomic Profiling of Hepatocellular Adenomas Paves the Way to Diagnostic and Prognostic Approaches. Hepatology, 74(3):1595-1610(2021) [pubmed]

10.1016/J.JHEPR.2023.100913;

10.1002/hep.31826;

submitter keyword: laser microdissection, tumor heterogeneity, proteomics,hepatocellular adenomas

Anne-Aurelie Raymond
contact affiliation	Plateforme Oncoprot, TBM-Core US 005, F-33000 Bordeaux, France
contact email	anne-aurelie.raymond@inserm.fr
lab head
Dupuy Jean-William
contact affiliation	Plateforme Proteome Bordeaux
contact email	jean-william.dupuy@u-bordeaux.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031323
     1. Label: PRIDE project
     2. Name: Characterization of tumor heterogeneity in beta-catenin mutated hepatocellular adenomas