September 22, 2019  |  

Interaction between the microbiome and TP53 in human lung cancer.

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

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.

Journal: Genome biology
DOI: 10.1186/s13059-018-1501-6
Year: 2018

Read publication

Talk with an expert

If you have a question, need to check the status of an order, or are interested in purchasing an instrument, we're here to help.