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Related Experiment Video

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Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
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Biliary Tract Carcinogenesis Model Based on Bile Metaproteomics.

Ariel A Arteta1,2,3, Miryan Sánchez-Jiménez4, Diego F Dávila5

  • 1School of Graduate Studies, CES University, Medellín, Colombia.

Frontiers in Oncology
|August 15, 2020
PubMed
Summary

This study reveals distinct human and bacterial proteomic profiles in bile from pancreatic cancer patients, suggesting bacteria drive biliary tract carcinogenesis through a dysbiotic microenvironment and biofilm formation.

Keywords:
IL-8bilecarcinogenesis modelmetaproteomicpancreatic cancerproteomicsurfactinzeatin

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Area of Science:

  • Metabolomics
  • Proteomics
  • Microbiology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) arises in a complex microenvironment.
  • Understanding the role of microbial and host factors in PDAC is crucial for early detection and treatment.

Purpose of the Study:

  • To compare human and bacterial proteomic profiles in bile from patients with pancreatic cancer versus gallstones.
  • To identify molecular differences associated with tumor versus non-tumor microenvironments in the biliary tract.
  • To propose a novel model for bacterial-induced carcinogenesis in the biliary tract.

Main Methods:

  • Liquid chromatography-mass spectrometry (LC-MS) was used to analyze proteomic profiles of bile samples from PDAC and gallstone (GS) patients.
  • Bioinformatic analysis using g:Profiler and KEGG Mapper identified over-represented biological and interaction pathways.
  • Comparative analysis focused on human and bacterial protein differences between tumor and non-tumor bile environments.

Main Results:

  • Three bacterial infection pathways were significantly over-represented in the PDAC group, with IL-8 identified as a key human protein.
  • Distinct qualitative and quantitative differences in bacterial proteins indicated a dysbiotic microenvironment in PDAC, including antibiotic biosynthesis enzymes.
  • Specific bacterial signaling molecules, zeatin (GS group) and surfactin (PDAC group), were identified, influencing key metabolic and quorum sensing pathways.

Conclusions:

  • This study presents the first metaproteomic comparison of human and bacterial bile proteins in tumor versus non-tumor settings.
  • A novel bacterial-induced carcinogenesis model for the biliary tract is proposed, highlighting the role of a long-lasting dysbiotic and harmful microenvironment.
  • Bacteria, particularly through biofilm formation in a dysbiotic environment, are suggested as key players in biliary tract carcinogenesis, warranting further in vitro and in vivo investigation.