Dataset Information

Liquid biopsy protein biomarkers of cholangiocarcinoma risk, early diagnosis and survival mirroring tumor cells - timsTOF (1/2)

ABSTRACT: 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 EVprognostic 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.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Primary Sclerosing Cholangitis,Cholangiocarcinoma

SUBMITTER: Mikel Azkargorta

LAB HEAD: Felix Elortza

PROVIDER: PXD036943 | Pride | 2023-07-20

REPOSITORIES: Pride

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			Action	DRS
	190_220523_Lapitz_New_1_S1-A1_1_3441.d.7z	Other
	190_220523_Lapitz_New_1_S1-A1_1_3441.mgf	Mgf
	191_220523_Lapitz_New_2_S1-A2_1_3442.d.7z	Other
	191_220523_Lapitz_New_2_S1-A2_1_3442.mgf	Mgf
	192_220523_Lapitz_New_3_S1-A3_1_3443.d.7z	Other

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Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma.

Lapitz Ainhoa A Azkargorta Mikel M Milkiewicz Piotr P Olaizola Paula P Zhuravleva Ekaterina E Grimsrud Marit M MM Schramm Christoph C Arbelaiz Ander A O'Rourke Colm J CJ La Casta Adelaida A Milkiewicz Malgorzata M Pastor Tania T Vesterhus Mette M Jimenez-Agüero Raul R Dill Michael T MT Lamarca Angela A Valle Juan W JW Macias Rocio I R RIR Izquierdo-Sanchez Laura L Pérez Castaño Ylenia Y Caballero-Camino Francisco Javier FJ Riaño Ioana I Krawczyk Marcin M Ibarra Cesar C Bustamante Javier J Nova-Camacho Luiz M LM Falcon-Perez Juan M JM Elortza Felix F Perugorria Maria J MJ Andersen Jesper B JB Bujanda Luis L Karlsen Tom H TH Folseraas Trine T Rodrigues Pedro M PM Banales Jesus M JM

Journal of hepatology 20230301 1

<h4>Background & aims</h4>Cholangiocarcinoma (CCA), heterogeneous biliary tumours with dismal prognosis, lacks accurate early diagnostic methods especially important for individuals at high-risk (i.e. those with primary sclerosing cholangitis [PSC]). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs).<h4>Methods</h4>EVs from patients with isolated PSC (n = 45), concomitant PSC-CCA (n = 44), PSC who developed CCA during follow-up (PSC to CCA; n = 25), CCAs from non-PSC ...[more]

PMID: 36868481

Similar Datasets

Project 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 EVprognostic 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.