Abstract 2907: A metaproteomic approach to study the host-microbiota interaction in cancer tissue

Abstract

Abstract Background: The microbiota has the ability to modulate cancer susceptibility through a systemic interaction with the host that occurs also at tissue level. Unraveling the functional meaning of the microbiota in the tumoral microenvironment is crucial to understand its causal role. Metagenomic approaches identify the microbial composition but not its functional role. In this study, we exploited a metaproteomic approach to investigate the presence of microbiota-derived proteins on breast cancer (BC) tumoral and healthy tissues using formalin-fixed paraffin-embedded (FFPE) samples, and to assess the interaction with human proteome Material and methods: Three tumoral regions (peripheral tumor, tumor core, in situ carcinoma) and 2 healthy areas (intra-tumoral fibrosis, healthy tissue) were selected on 5 FFPE BC samples, 3 triple negative and 2 luminal, chosen based on the year of inclusion in FFPE (2017-2018). The proteomic analysis was performed on 10 µm tissue slides, by nanoLC-MS/MS analysis and data analysis by Perseus and Maxquant. Results: The proteomic analysis revealed the presence of 13 microbial proteins. Seven proteins are involved in energy production and metabolism, 4 are chaperonins. Most of the proteins were found in the intra tumoral fibrosis. Two Chaperone proteins DnaK (Thermosipho melanesiensis etc. and Rhodothermus marinus) and an S-adenosylmethionine synthase (MAT2A) (Homo sapiens; Helicobacter hepaticus etc.) were overexpressed in tumor tissue compared to the healthy. 1073 human proteins were identified and 78 were overexpressed. KEGG analysis revealed that the proteins overexpressed in healthy tissues are involved in the maintenance of cell and tissue structure and function, protein digestion and absorption, mediator of innate immunity and nonspecific defense mechanism against pathogens. The proteins overexpressed in tumor tissues belong to protein processing, antigen processing and presentation, carbon metabolism and phagosome or E.coli infection pathways Discussion: A proteomic approach on tumor tissue can give functional information about the host-microbiota interactions. Our preliminary data shows an overexpression in tumor samples, in particular in intra tumoral fibrosis, of DnaKs and MAT2A. The first are bacterial chaperone proteins able to interfere with important pathways related to DNA damage control/repair, cell-cycle/apoptosis and is a cancer promoter. The second protein is an enzyme essential for methylation that can confer growth and survival advantage to cancerous cells, enhancing tumor migration. Most of the bacterial proteins identified are involved in energy production or chaperonins. Taken together the bacterial and human proteome results, it seems that bacteria supply the tumor cells with important proteins that promote cancer growth and which fit perfectly into the pathways most represented in the tumor. More studies are needed to confirm the hypothesis. Citation Format: Francesca Pirini, Tania Rossi, Soulaimane Aboulouard, Giovanni Martinelli, Sara Bravaccini, Michel Salzet. A metaproteomic approach to study the host-microbiota interaction in cancer tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2907.