AUTHOR=Arteta Ariel A. , Sánchez-Jiménez Miryan , Dávila Diego F. , Palacios Oscar G. , Cardona-Castro Nora 

TITLE=Biliary Tract Carcinogenesis Model Based on Bile Metaproteomics

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01032

DOI=10.3389/fonc.2020.01032

ISSN=2234-943X

ABSTRACT=Purpose: To analyze human and bacteria proteomic profiles in bile, exposed to a tumor vs. non-tumor microenvironment, in order to identify differences between these conditions, which may contribute to a better understanding of pancreatic carcinogenesis. 
Patients and Methods: Using liquid chromatography and mass spectrometry, human and bacteria proteomic profiles of a total of 20 bile samples (7 from gallstone (GS) patients, and 13 from pancreatic head ductal adenocarcinoma (PDAC) patients) that were collected during surgery, and taken directly from the gallbladder were compared. g: Profiler and KEGG (Kyoto Encyclopedia of Genes and Genomes) Mapper Reconstruct Pathway was used as the main comparative platform focusing on over-represented biological pathways among human proteins and interaction pathways among bacterial proteins.
Results: Three bacterial infection pathways were over-represented in the human PDAC group of proteins. IL-8 is the only human protein that coincides in the three pathways, and this protein is only present in the PDAC group. Quantitative and qualitative differences in bacterial proteins suggest a dysbiotic microenvironment in the PDAC group, supported by major participation of antibiotic biosynthesis enzymes. Prokaryote interaction signaling pathways highlight the presence of zeatin in the GS group and surfactin in the PDAC group, the former in the metabolism of terpenoids and polyketides, and the latter in both metabolism of terpenoids, polyketides, and quorum sensing. Based on our findings, we propose a bacterial-induced carcinogenesis model for the biliary tract.
Conclusion: To the best of our knowledge, this is the first study to compare human and bacteria bile proteins in a tumor vs. non-tumor microenvironment. Our results suggest that bacteria may be key players in biliary tract carcinogenesis in a long-lasting dysbiotic and harmful epithelial microenvironment, in which specific bacterial species biofilm formation is of utmost importance. Our finding should be further explored in future using in vitro and in vivo investigations