Back to Search
Start Over
Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer
- Source :
- American Journal of Respiratory and Critical Care Medicine. 198:1188-1198
- Publication Year :
- 2018
- Publisher :
- American Thoracic Society, 2018.
-
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.
- Subjects :
- Adult
Male
0301 basic medicine
Pulmonary and Respiratory Medicine
Lung Neoplasms
Respiratory System
Critical Care and Intensive Care Medicine
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Bronchoscopy
medicine
Humans
Prospective Studies
Microbiome
Lung cancer
PI3K/AKT/mTOR pathway
Aged
Original Research
business.industry
Cell growth
Microbiota
Middle Aged
respiratory system
medicine.disease
respiratory tract diseases
Up-Regulation
Cross-Sectional Studies
030104 developmental biology
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Cancer research
Tissue invasion
Female
business
Airway
Subjects
Details
- ISSN :
- 15354970 and 1073449X
- Volume :
- 198
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....5f8082e617849fc779612c906de51760