Journal article
Interaction between the microbiome and TP53 in human lung cancer
Genome biology, v 19(1), pp 123-123
24 Aug 2018
PMID: 30143034
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Lung 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.
Overall, 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.
The 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.
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Details
- Title
- Interaction between the microbiome and TP53 in human lung cancer
- Creators
- K Leigh Greathouse - Present Address: Nutrition Sciences, Baylor University, Waco, TX, 97346, USAJames R White - Resphera Biosciences, Baltimore, MD, 21231, USAAshely J Vargas - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USAValery V Bliskovsky - Center for Cancer Research Genomics Core, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USAJessica A Beck - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USANatalia von Muhlinen - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USAEric C Polley - Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 55905, USAElise D Bowman - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USAMohammed A Khan - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USAAna I Robles - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USATomer Cooks - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USABríd M Ryan - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USANoah Padgett - Department of Educational Psychology, Baylor University, Waco, TX, 97346, USAAmiran H Dzutsev - Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USAGiorgio Trinchieri - Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USAMarbin A Pineda - Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, Bethesda, MD, 20892, USASven Bilke - Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, Bethesda, MD, 20892, USAPaul S Meltzer - Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, Bethesda, MD, 20892, USAAlexis N Hokenstad - Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USATricia M Stickrod - Microbiome Laboratory, Mayo Clinic, Rochester, MN, 55905, USAMarina R Walther-Antonio - Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USAJoshua P Earl - Department of Microbiology and Immunology, Center for Genomic Sciences, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 19129, USAJoshua C Mell - Department of Microbiology and Immunology, Center for Genomic Sciences, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 19129, USAJaroslaw E Krol - Department of Microbiology and Immunology, Center for Genomic Sciences, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 19129, USASergey V Balashov - Department of Microbiology and Immunology, Center for Genomic Sciences, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 19129, USAArchana S Bhat - Department of Microbiology and Immunology, Center for Genomic Sciences, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 19129, USAGarth D Ehrlich - Department of Microbiology and Immunology, Center for Genomic Sciences, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 19129, USAAlex Valm - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USAClayton Deming - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USASean Conlan - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USAJulia Oh - Jackson Laboratory, Framingham, CT, 06032, USAJulie A Segre - National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USACurtis C Harris - Laboratory of Human Carcinogenesis, Center for Cancer, Research, National Cancer Institute, National Institutes of Health, 37 Convent Dr., Rm 3068A, MSC 4258, Bethesda, MD, 20892-4258, USA. curtis_harris@nih.gov
- Publication Details
- Genome biology, v 19(1), pp 123-123
- Publisher
- Springer BMC; England
- Grant note
- P30 CA034196 / NCI NIH HHS Intramural / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000442559800001
- Scopus ID
- 2-s2.0-85052057198
- Other Identifier
- 991014969876204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Genetics & Heredity