Interaction between the microbiome and TP53 in human lung cancer.

Genome Biology
K Leigh GreathouseCurtis C Harris

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 ...Continue Reading

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Methods Mentioned

BETA
biopsy
RNA-seq
lavage
dissection
PCR
chips

Software Mentioned

MetaPhlAn
MiSeq
PacBio Binding Calculator
RS Dashboard
Imaris
USEARCH61
Bowtie2
BLASTN
Stata
ImagePro Plus

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