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RNA profiles in serum and urine extracellular vesicles of patients with cholangiocarcinoma mimicking tumor expression: novel liquid biopsy approach

ABSTRACT: RNA profiles in serum and urine extracellular vesicles of patients with cholangiocarcinoma mimicking tumor expression: novel liquid biopsy approach

PROVIDER: PRJNA603909 | ENA |

REPOSITORIES: ENA

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RNA profiles in serum and urine extracellular vesicles of patients with cholangiocarcinoma mimicking tumor expression: novel liquid biopsy approach

Project description:Cholangiocarcinoma (CCA) represents a heterogeneous group of biliary cancers with poor prognosis. Although the aetiology is generally unknown, factors like Primary Sclerosing Cholangitis (PSC) predispose to its development. Simultaneously, around 80% of patients with PSC have concomitant Ulcerative Colitis (UC). As there are no specific and sensitive biomarkers for the non-invasive diagnosis of CCA, we aimed to analyse the RNA content of serum and urine extracellular vesicles (EVs) to find accurate biomarkers of CCA that could be reflecting tumor behaviour. The transcriptomic analysis of these EVs showed a differential profile of RNAs in patients with CCA compared to healthy individuals or patients with other diseases (PSC and UC), presenting some RNAs high diagnostic values to distinguish patients with CCA. Moreover, the differential abundance of several RNAs in serum and/or urine EVs correlated with the deregulated expression of those transcripts in CCA tissue compared to surrounding liver (TCGA and Copenhagen cohorts), in tumor (EGI1, TFK1) and normal cholangiocyte (NHC) cell lines as well as in EVs secreted by those cell lines; pinpointing the potential involvement of those RNAs not only as liquid biopsy biomarkers but also as potential mediators of CCA pathogenesis.

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Pre-analytical factors affecting the establishment of a single tube assay for multi-parameter liquid biopsy detection in melanoma patients

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Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a ‘liquid gold’ biopsy

Project description:Background: Biomarkers that reflect glioblastoma tumour activity and treatment response are urgently needed to help guide clinical management, particularly for recurrent disease. As the urinary system is a major clearance route of circulating extracellular vesicles (EVs; 30-1000 nm nanoparticles) we explored whether sampling urinary-EVs could serve as a simple and non-invasive liquid biopsy approach for measuring glioblastoma-associated biomarkers. Methods: Fifty urine specimens (15-60 ml) were collected from 24 catheterised glioblastoma patients immediately prior to primary (n=17) and recurrence (n=7) surgeries, following gross total resection (n=9), and from age/gender-matched healthy participants (n=14). EVs isolated by differential ultracentrifugation were characterised and extracted proteomes were analysed by high-resolution data-independent acquisition liquid chromatography tandem mass spectrometry (DIA-LC-MS/MS). Results: Overall, 6857 proteins were confidently identified in urinary-EVs (q-value≤0.01), including 94 EV marker proteins. Glioblastoma-specific proteomic signatures were determined, and putative urinary-EV biomarkers corresponding to tumour burden and recurrence were identified (FC≥|2|, adjust p-val≤0.05, AUC>0.9). Conclusion: In-depth DIA-LC-MS/MS characterisation of urinary-EVs substantiates urine as a viable source of glioblastoma biomarkers. The promising ‘liquid gold’ biomarker panels described here warrant further investigation.

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High-throughput screening of gene expression in the patient's cholangiocarcinoma biopsy

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Evaluating Liquid Biopsies for Methylomic Profiling of Prostate Cancer

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