PXD036943

PXD036943 is an original dataset announced via ProteomeXchange.

Title	Liquid biopsy protein biomarkers of cholangiocarcinoma risk, early diagnosis and survival mirroring tumor cells - timsTOF (1/2)
Description	Background Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EV prognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.
HostingRepository	PRIDE
AnnounceDate	2023-07-20
AnnouncementXML	Submission_2023-07-20_14:22:42.023.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036943
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	MikelAzkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-22 00:30:23	ID requested
⏵ 1	2023-07-20 14:22:42	announced

10.6019/PXD036943;

Lapitz A, Azkargorta M, Milkiewicz P, Olaizola P, Zhuravleva E, Grimsrud MM, Schramm C, Arbelaiz A, O'Rourke CJ, La Casta A, Milkiewicz M, Pastor T, Vesterhus M, Jimenez-Ag, ü, ero R, Dill MT, Lamarca A, Valle JW, Macias RIR, Izquierdo-Sanchez L, P, é, rez Casta, ñ, o Y, Caballero-Camino FJ, Ria, ñ, o I, Krawczyk M, Ibarra C, Bustamante J, Nova-Camacho LM, Falcon-Perez JM, Elortza F, Perugorria MJ, Andersen JB, Bujanda L, Karlsen TH, Folseraas T, Rodrigues PM, Banales JM, Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma. J Hepatol, 79(1):93-108(2023) [pubmed]

submitter keyword: Cholangiocarcinoma

extracellular vesicles

primary sclerosing cholangitis

biomarkers

liquid biopsy

single-cell RNA-sequencing

mass spectrometry

FelixElortza
contact affiliation	Proteomics Service CIC bioGUNE Bizkaia Tech. Park Build. 800 48160 Derio (Spain)
contact email	felortza@cicbiogune.es
lab head
MikelAzkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036943
     1. Label: PRIDE project
     2. Name: Liquid biopsy protein biomarkers of cholangiocarcinoma risk, early diagnosis and survival mirroring tumor cells - timsTOF (1/2)