Interaction between the microbiome and TP53 in human lung cancer

K. Leigh Greathouse, James R. White, Ashely J. Vargas, Valery V. Bliskovsky, Jessica A. Beck, Natalia von Muhlinen, Eric 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. StickrodMarina 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

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number123
JournalGenome Biology
Volume19
Issue number1
DOIs
StatePublished - Aug 24 2018

Fingerprint

Microbiota
lung neoplasms
cancer
Lung Neoplasms
neoplasms
Comamonadaceae
Acidovorax
tumor
Neoplasms
squamous cell carcinoma
Squamous Cell Carcinoma
cigarettes
mutation
lungs
smoke
Smoke
Tobacco Products
Lung
Mutation
ribosomal RNA

Keywords

  • Lung cancer
  • Microbiome
  • Mutation
  • Squamous cell carcinoma
  • TP53

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

Cite this

Greathouse, K. L., White, J. R., Vargas, A. J., Bliskovsky, V. V., Beck, J. A., von Muhlinen, N., ... Harris, C. C. (2018). Interaction between the microbiome and TP53 in human lung cancer. Genome Biology, 19(1), [123]. https://doi.org/10.1186/s13059-018-1501-6

Interaction between the microbiome and TP53 in human lung cancer. / Greathouse, K. Leigh; White, James R.; Vargas, Ashely J.; Bliskovsky, Valery V.; Beck, Jessica A.; von Muhlinen, Natalia; Polley, Eric; Bowman, Elise D.; Khan, Mohammed A.; Robles, Ana I.; Cooks, Tomer; Ryan, Bríd M.; Padgett, Noah; Dzutsev, Amiran H.; Trinchieri, Giorgio; Pineda, Marbin A.; Bilke, Sven; Meltzer, Paul S.; Hokenstad, Alexis N.; Stickrod, Tricia M.; Walther-Antonio, Marina; Earl, Joshua P.; Mell, Joshua C.; Krol, Jaroslaw E.; Balashov, Sergey V.; Bhat, Archana S.; Ehrlich, Garth D.; Valm, Alex; Deming, Clayton; Conlan, Sean; Oh, Julia; Segre, Julie A.; Harris, Curtis C.

In: Genome Biology, Vol. 19, No. 1, 123, 24.08.2018.

Research output: Contribution to journalArticle

Greathouse, KL, White, JR, Vargas, AJ, Bliskovsky, VV, Beck, JA, von Muhlinen, N, Polley, E, Bowman, ED, Khan, MA, Robles, AI, Cooks, T, Ryan, BM, Padgett, N, Dzutsev, AH, Trinchieri, G, Pineda, MA, Bilke, S, Meltzer, PS, Hokenstad, AN, Stickrod, TM, Walther-Antonio, M, Earl, JP, Mell, JC, Krol, JE, Balashov, SV, Bhat, AS, Ehrlich, GD, Valm, A, Deming, C, Conlan, S, Oh, J, Segre, JA & Harris, CC 2018, 'Interaction between the microbiome and TP53 in human lung cancer', Genome Biology, vol. 19, no. 1, 123. https://doi.org/10.1186/s13059-018-1501-6
Greathouse KL, White JR, Vargas AJ, Bliskovsky VV, Beck JA, von Muhlinen N et al. Interaction between the microbiome and TP53 in human lung cancer. Genome Biology. 2018 Aug 24;19(1). 123. https://doi.org/10.1186/s13059-018-1501-6
Greathouse, K. Leigh ; White, James R. ; Vargas, Ashely J. ; Bliskovsky, Valery V. ; Beck, Jessica A. ; von Muhlinen, Natalia ; Polley, Eric ; Bowman, Elise D. ; Khan, Mohammed A. ; Robles, Ana I. ; Cooks, Tomer ; Ryan, Bríd M. ; Padgett, Noah ; Dzutsev, Amiran H. ; Trinchieri, Giorgio ; Pineda, Marbin A. ; Bilke, Sven ; Meltzer, Paul S. ; Hokenstad, Alexis N. ; Stickrod, Tricia M. ; Walther-Antonio, Marina ; Earl, Joshua P. ; Mell, Joshua C. ; Krol, Jaroslaw E. ; Balashov, Sergey V. ; Bhat, Archana S. ; Ehrlich, Garth D. ; Valm, Alex ; Deming, Clayton ; Conlan, Sean ; Oh, Julia ; Segre, Julie A. ; Harris, Curtis C. / Interaction between the microbiome and TP53 in human lung cancer. In: Genome Biology. 2018 ; Vol. 19, No. 1.
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AU - Greathouse, K. Leigh

AU - White, James R.

AU - Vargas, Ashely J.

AU - Bliskovsky, Valery V.

AU - Beck, Jessica A.

AU - von Muhlinen, Natalia

AU - Polley, Eric

AU - Bowman, Elise D.

AU - Khan, Mohammed A.

AU - Robles, Ana I.

AU - Cooks, Tomer

AU - Ryan, Bríd M.

AU - Padgett, Noah

AU - Dzutsev, Amiran H.

AU - Trinchieri, Giorgio

AU - Pineda, Marbin A.

AU - Bilke, Sven

AU - Meltzer, Paul S.

AU - Hokenstad, Alexis N.

AU - Stickrod, Tricia M.

AU - Walther-Antonio, Marina

AU - Earl, Joshua P.

AU - Mell, Joshua C.

AU - Krol, Jaroslaw E.

AU - Balashov, Sergey V.

AU - Bhat, Archana S.

AU - Ehrlich, Garth D.

AU - Valm, Alex

AU - Deming, Clayton

AU - Conlan, Sean

AU - Oh, Julia

AU - Segre, Julie A.

AU - Harris, Curtis C.

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