Interaction between the microbiome and TP53 in human lung cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08-24

AUTHORS

K. Leigh Greathouse, James R. White, Ashely J. Vargas, Valery V. Bliskovsky, Jessica A. Beck, Natalia von Muhlinen, Eric C. Polley, Elise D. Bowman, Mohammed A. Khan, Ana I. Robles, Tomer Cooks, Bríd M. Ryan, Noah Padgett, Amiran H. Dzutsev, Giorgio Trinchieri, Marbin A. Pineda, Sven Bilke, Paul S. Meltzer, Alexis N. Hokenstad, Tricia M. Stickrod, Marina R. Walther-Antonio, Joshua P. Earl, Joshua C. Mell, Jaroslaw E. Krol, Sergey V. Balashov, Archana S. Bhat, Garth D. Ehrlich, Alex Valm, Clayton Deming, Sean Conlan, Julia Oh, Julie A. Segre, Curtis C. Harris

ABSTRACT

BackgroundLung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort.ResultsOverall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas.ConclusionsThe results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection. More... »

PAGES

123

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  • Journal

    TITLE

    Genome Biology

    ISSUE

    1

    VOLUME

    19

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13059-018-1501-6

    DOI

    http://dx.doi.org/10.1186/s13059-018-1501-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106329087

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30143034


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    511 Present Address: Nutrition Sciences, Baylor University, 97346, Waco, TX, USA
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    530 Department of Surgery, Mayo Clinic, 55905, Rochester, MN, USA
    531 Division of Biomedical Statistics and Informatics, Mayo Clinic, 55905, Rochester, MN, USA
    532 Microbiome Laboratory, Mayo Clinic, 55905, Rochester, MN, USA
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