PXD051527

PXD051527 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling in fibrolamellar carcinoma patient tumor tissue
Description	Fibrolamellar carcinoma (FLC) is a rare, early-onset liver cancer. The five-year survival rate is low, and there is a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets. To date, only one study has attempted to characterize the FLC proteome and metabolome, but with modest sample size (proteomics—n = 16 patient samples; metabolomics—n = 10 patient samples) and protein detection (n = 4620 proteins). We have performed the most comprehensive characterization of FLC in both proteomics (n = 23 patient samples; n = 8485 proteins) and metabolomics (n = 26 patient samples; n = 135 metabolites). Additionally, we have conducted respirometry analyses as well as RNAi- and small molecule inhibitor-mediated loss of function assays in FLC tumors and non-malignant liver tissue from patients. We propose a model of cellular energetics in FLC that centers on amino acids. Our model points to proline anabolism that is very likely mediated by ornithine aminotransferase hyperactivity and ornithine transcarbamylase hypoactivity with serine and glutamine catabolism providing the starting substrate. The metabolic rewiring in FLC proposed by our model, with a particular emphasis on mitochondria, can be exploited for therapeutic vulnerabilities.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_15:03:07.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	José Eduardo Araújo
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	2024-04-17 05:28:54	ID requested
⏵ 1	2025-05-06 15:03:08	announced

10.1016/j.xcrm.2024.101699;

Long D, Chan M, Han M, Kamdar Z, Ma RK, Tsai PY, Francisco AB, Barrow J, Shackelford DB, Yarchoan M, McBride MJ, Orre LM, Vacanti NM, Gujral TS, Sethupathy P, Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma. Cell Rep Med, 5(9):101699(2024) [pubmed]

submitter keyword: primary, cancer, FLC, non-malignant, human, liver,Fibrolamellar Carcinoma, frozen tissue, metastatic

Janne Lehtiö
contact affiliation	Department of Oncology-Pathology, Karolinska Institutitet
contact email	janne.lehtio@ki.se
lab head
José Eduardo Araújo
contact affiliation	Clinical Proteomics Mass Spectrometry, SciLifeLab, Karolinska Institutet
contact email	jose-eduardo.araujo@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/PXD051527

PRIDE project URI

• PRIDE
  1. PXD051527
     1. Label: PRIDE project
     2. Name: Proteomic profiling in fibrolamellar carcinoma patient tumor tissue