ArticleJournal of biomedical science2020
Bile and urine peptide marker profiles: access keys to molecular pathways and biological processes in cholangiocarcinoma.
Article in Journal of biomedical science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- A Comprehensive Review on Capillary Electrophoresis-Mass Spectrometry in Advancing Biomolecular Research.Electrophoresis · 2025Review
- Peptide Biomarkers - An Emerging Diagnostic Tool and Current Applicable Assay.Current protein & peptide science · 2025Review
- Emerging insights into ferroptosis in cholangiocarcinoma (Review).Oncology letters · 2024Review
- Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration.Frontiers in pharmacology · 2024Article
- Recent Advances of Proteomics in Management of Acute Kidney Injury.Diagnostics (Basel, Switzerland) · 2023Review
- Identification of a novel bile marker clusterin and a public online prediction platform based on deep learning for cholangiocarcinoma.BMC medicine · 2023Article
- Review
- New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming.Journal of experimental & clinical cancer research : CR · 2022Article
- Current applications of capillary electrophoresis-mass spectrometry for the analysis of biologically important analytes in urine (2017 to mid-2021): A review.Journal of separation science · 2022Review
- Mast cells in liver disease progression: An update on current studies and implications.Hepatology (Baltimore, Md.) · 2022Review
- Article
- Article
- Role of Endoscopy in Primary Sclerosing Cholangitis.Clinical endoscopy · 2021Review
- Biliary Strictures and Cholangiocarcinoma - Untangling a Diagnostic Conundrum.Frontiers in oncology · 2021Review
- Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach.Cancers · 2020Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDetection of cholangiocarcinoma (CCA) remains a diagnostic challenge. We established diagnostic peptide biomarkers in bile and urine based on capillary electrophoresis coupled to mass spectrometry (CE-MS) to detect both local and systemic changes during CCA progression. In a prospective cohort study we recently demonstrated that combined bile and urine proteome analysis could further improve diagnostic accuracy of CCA diagnosis in patients with unknown biliary strictures. As a continuation of these investigations, the aim of the present study was to investigate the pathophysiological mechanisms behind the molecular determinants reflected by bile and urine peptide biomarkers.
methodsProtease mapping and gene ontology cluster analysis were performed for the previously defined CE-MS based biomarkers in bile and urine. For that purpose, bile and urine peptide profiles (from samples both collected at the date of endoscopy) were investigated from a representative cohort of patients with benign (n = 76) or CCA-associated (n = 52) biliary strictures (verified during clinical follow-up). This was supplemented with a literature search for the association of the individual biomarkers included in the proteomic patterns with CCA or cancer progression.
resultsFor most of the peptide markers, association to CCA has been described in literature. Protease mapping revealed ADAMTS4 activity in cleavage of both bile and urine CCA peptide biomarkers. Furthermore, increased chymase activity in bile points to mast cell activation at the tumor site. Gene ontology cluster analysis indicates cellular response to chemical stimuli and stress response as local and extracellular matrix reorganization by tissue destruction and repair as systemic events. The analysis further supports that the mapped proteases are drivers of local and systemic events.
conclusionsThe study supports connection of the CCA-associated peptide biomarkers to the molecular pathophysiology and indicates an involvement in epithelial-to-mesenchymal transition, generation of cancer-associated fibroblasts and activation of residual immune cells. Proteases, extracellular matrix components, inflammatory cytokines, proangiogenic, growth and vasoactive factors released from the tumor microenvironment are drivers of systemic early events during CCA progression.
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