Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

被引：72

作者：

Lapitz, Ainhoa ^{[1
]}

Arbelaiz, Ander ^{[1
]}

O'Rourke, Colm J. ^{[2
]}

Lavin, Jose L. ^{[3
]}

La Casta, Adelaida ^{[1
]}

Ibarra, Cesar ^{[4
]}

Jimeno, Juan P. ^{[5
]}

Santos-Laso, Alvaro ^{[1
]}

Izquierdo-Sanchez, Laura ^{[1
,6
]}

Krawczyk, Marcin ^{[7
,8
]}

Perugorria, Maria J. ^{[1
,6
]}

Jimenez-Aguero, Raul ^{[1
]}

Sanchez-Campos, Alberto ^{[4
]}

Riano, Ioana ^{[1
]}

Gonzalez, Esperanza ^{[9
]}

Lammert, Frank ^{[7
]}

Marzioni, Marco ^{[10
]}

Macias, Rocio I. R. ^{[6
,11
]}

Marin, Jose J. G. ^{[6
,11
]}

Karlsen, Tom H. ^{[12
]}

Bujanda, Luis ^{[1
,6
]}

Falcon-Perez, Juan M. ^{[6
,9
,13
]}

Andersen, Jesper B. ^{[2
]}

Aransay, Ana M. ^{[3
,6
]}

Rodrigues, Pedro M. ^{[1
]}

Banales, Jesus M. ^{[1
,6
,13
]}

机构：

[1] Univ Basque Country, Donostia Univ Hosp, Biodonostia Hlth Res Inst, Dept Liver & Gastrointestinal Dis,UPV EHU, San Sebastian 20014, Spain

[2] BRIC, Dept Hlth & Med Sci, DK-2200 Copenhagen, Denmark

[3] CIC bioGUNE, Genome Anal Platform, Derio 48160, Spain

[4] Hosp Cruces, Bilbao 48903, Spain

[5] Complejo Hosp Navarra, Pamplona 31008, Spain

[6] Carlos III Natl Inst Hlth, Ctr Study Liver & Gastrointestinal Dis CIBERehd, Madrid 28220, Spain

[7] Saarland Univ, Med Ctr, Dept Med 2, D-66421 Homburg, Germany

[8] Ctr Preclin Res, Dept Gen Transplant & Liver Surg, Lab Metab Liver Dis, PL-02091 Warsaw, Poland

[9] Ctr Cooperat Res Biosci CIC bioGUNE, Exosomes Lab, BRTA, Derio 48160, Spain

[10] Univ Politecn Marche, Dept Gastroenterol, I-60121 Ancona, Italy

[11] Biomed Res Inst Salamanca IBSAL, Expt Hepatol & Drug Targeting HEVEFARM, Salamanca 37007, Spain

[12] Oslo Univ Hosp, Norwegian PSC Res Ctr, Div Canc Med Surg & Transplantat, Oslo 0372, Spain

[13] Basque Fdn Sci, Ikerbasque, Bilbao 48013, Spain

来源：

CELLS | 2020年 / 9卷 / 03期

基金：

英国医学研究理事会; 欧盟地平线“2020”;

关键词：

biomarkers; cholangiocarcinoma; extracellular vesicles; liquid biopsy; transcriptomics; PRIMARY SCLEROSING CHOLANGITIS; POOR-PROGNOSIS; GASTRIC-CANCER; UP-REGULATION; METASTASIS; INVASION; PROMOTES; KINASE; DAMAGE; PROLIFERATION;

D O I：

10.3390/cells9030721

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.

引用

页数：33

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