Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer
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A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
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- Teacher spread
- 0.289 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
RATIONALE: In lung cancer, upregulation of the PI3K (phosphoinositide 3-kinase) pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals. OBJECTIVES: We hypothesize that host-microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways. METHODS: Airway brushings were collected prospectively from subjects with lung nodules at time of diagnostic bronchoscopy, including 39 subjects with final lung cancer diagnoses and 36 subjects with noncancer diagnoses. In addition, samples from 10 healthy control subjects were included. 16S ribosomal RNA gene amplicon sequencing and paired transcriptome sequencing were performed on all airway samples. In addition, an in vitro model with airway epithelial cells exposed to bacteria/bacterial products was performed. MEASUREMENTS AND MAIN RESULTS: The composition of the lower airway transcriptome in the patients with cancer was significantly different from the control subjects, which included up-regulation of ERK (extracellular signal-regulated kinase) and PI3K signaling pathways. The lower airways of patients with lung cancer were enriched for oral taxa (Streptococcus and Veillonella), which was associated with up-regulation of the ERK and PI3K signaling pathways. In vitro exposure of airway epithelial cells to Veillonella, Prevotella, and Streptococcus led to upregulation of these same signaling pathways. CONCLUSIONS: The data presented here show that several transcriptomic signatures previously identified as relevant to lung cancer pathogenesis are associated with enrichment of the lower airway microbiota with oral commensals.
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The record
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Topic
- Gut microbiota and health
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- National Center for Advancing Translational SciencesNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Institutes of HealthYork UniversityClinical and Translational Science Institute, New York UniversityA Breath of Hope Lung FoundationSimons FoundationU.S. Department of Defense
- Keywords
- Lung cancerDownregulation and upregulationMedicineTranscriptomePrevotellaPI3K/AKT/mTOR pathwayMicrobiomeCancer researchImmunologyBiologyPathologySignal transductionBioinformaticsGene expressionCell biologyGeneBacteria
- Has abstract in OpenAlex
- yes