BRAF V600E mutation impinges on gut microbial markers defining novel biomarkers for serrated colorectal cancer effective
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(2020) 39:285
RESEARCH
Open Access
BRAFV600E mutation impinges on gut microbial markers defining novel biomarkers for serrated colorectal cancer effective therapies Nadia Trivieri1†, Riccardo Pracella1†, Maria Grazia Cariglia1, Concetta Panebianco2, Paola Parrella3, Alberto Visioli4, Fabrizio Giani4, Amata Amy Soriano1, Chiara Barile1, Giuseppe Canistro5, Tiziana Pia Latiano6, Lucia Dimitri7, Francesca Bazzocchi5, Dario Cassano5, Angelo L. Vescovi4,8, Valerio Pazienza2† and Elena Binda1,9*†
Abstract Background: Colorectal cancer (CRC) harboring BRAFV600E mutation exhibits low response to conventional therapy and poorest prognosis. Due to the emerging correlation between gut microbiota and CRC carcinogenesis, we investigated in serrated BRAFV600E cases the existence of a peculiar fecal microbial fingerprint and specific bacterial markers, which might represent a tool for the development of more effective clinical strategies. Methods: By injecting human CRC stem-like cells isolated from BRAFV600E patients in immunocompromised mice, we described a new xenogeneic model of this subtype of CRC. By performing bacterial 16S rRNA sequencing, the fecal microbiota profile was then investigated either in CRC-carrying mice or in a cohort of human CRC subjects. The microbial communities’ functional profile was also predicted. Data were compared with Mann-Whitney U, Welch’s t-test for unequal variances and Kruskal-Wallis test with Benjamini–Hochberg false discovery rate (FDR) correction, extracted as potential BRAF class biomarkers and selected as model features. The obtained mean test prediction scores were subjected to Receiver Operating characteristic (ROC) analysis. To discriminate the BRAF status, a Random Forest classifier (RF) was employed. (Continued on next page)
* Correspondence: [email protected] † Valerio Pazienza and Elena Binda these authors are share senior authorship. † Nadia Trivieri and Riccardo Pracella contributed equally. 1 Cancer Stem Cells Unit, ISBReMIT, IRCSS Casa Sollievo della Sofferenza, Opera di San Pio da Pietrelcina, San Giovanni Rotondo, FG, Italy 9 Cancer Stem Cells Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapeutics (ISBReMIT), 71013 San Giovanni Rotondo, FG, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory
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