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Record W2806389440 · doi:10.1164/rccm.201710-2118oc

Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer

2018· article· en· W2806389440 on OpenAlexfundno aff
Jun-Chieh J. Tsay, Benjamin G. Wu, Michelle Badri, José C. Clemente, Nan Shen, Peter Meyn, Yonghua Li, Ting-An Yie, Tenzin Lhakhang, Evan Olsen, Vivek Murthy, Gaëtane Michaud, Imran Sulaiman, Aristotelis Tsirigos, Adriana Heguy, Harvey I. Pass, Michael D. Weiden, William N. Rom, Daniel H. Sterman, Richard Bonneau, Martin J. Blaser, Leopoldo N. Segal

Bibliographic record

VenueAmerican Journal of Respiratory and Critical Care Medicine · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsnot available
FundersNational 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
KeywordsLung cancerDownregulation and upregulationMedicineTranscriptomePrevotellaPI3K/AKT/mTOR pathwayMicrobiomeCancer researchImmunologyBiologyPathologySignal transductionBioinformaticsGene expressionCell biologyGeneBacteria

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.298
Teacher spread0.289 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations457
Published2018
Admission routes1
Has abstractyes

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