Evidence map›Paper›PMID 22341411›Full record

ArticleLung cancer (Amsterdam, Netherlands)2012

Frequent downregulation of the transcription factor Foxa2 in lung cancer through epigenetic silencing.

Daniela S Basseres, Francesco D'Alò, Beow Y Yeap, Ester C Löwenberg, David A Gonzalez, Hiroyuki Yasuda, Tajhal Dayaram, Olivier N Kocher, John J Godleski, William G Richards and 5 more

Open access · greenAbstract read
In one paragraph

Article in Lung cancer (Amsterdam, Netherlands), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Dual Effect ofBiology · 2026
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  5. Review
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Correlation Between High Expression of FOXA2 and Improved Overall Survival in Ovarian Cancer Patients.Medical science monitor : international medical journal of experimental and clinical research · 2021
    Article
  13. Article
  14. Epigenetics of lung cancer: a translational perspective.Cellular oncology (Dordrecht, Netherlands) · 2019
    Review
  15. Article
  16. Article
  17. An Elusive Fox that Suppresses Scgb1a1 in Asthma Has Been Found.American journal of respiratory cell and molecular biology · 2019
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Daniela S BasseresBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; University of São Paulo, São Paulo, SP, Brazil.
Francesco D'Alò
Beow Y Yeap
Ester C Löwenberg
David A Gonzalez
Hiroyuki Yasuda
Tajhal Dayaram
Olivier N Kocher
John J Godleski
William G Richards
Matthew Meyerson
Susumu Kobayashi
Daniel G Tenen
Balázs Halmos
Daniel B Costa
Harvard University · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USColumbia University · US

Funding

Translational studies of Hsp90 inhibitors in NSCLCP50CA090578 · NCI · DANA-FARBER CANCER INST · PI YEAP, BEOW Y · 2008 to 2012
$11.4M
SPORE in Lung CancerP20CA090578 · NCI · DANA-FARBER CANCER INSTITUTE · PI JOHNSON, BRUCE E. · 2003 to 2007
$5.1M
Overcoming resistance to tyrosine kinase inhibitors in lung cancerR01CA169259 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KOBAYASHI, SUSUMU · 2013 to 2018
$1.8M
NCI NIH HHS CA090578NCI NIH HHS P20 CA090578NCI NIH HHS P50 CA090578NCI NIH HHS R01 CA169259
6 · The paper itself

Abstract

purposeWe sought to determine the mechanisms of downregulation of the airway transcription factor Foxa2 in lung cancer and the expression status of Foxa2 in non-small-cell lung cancer (NSCLC).

methodsA series of 25 lung cancer cell lines were evaluated for Foxa2 protein expression, FOXA2 mRNA levels, FOXA2 mutations, FOXA2 copy number changes and for evidence of FOXA2 promoter hypermethylation. In addition, 32 NSCLCs were sequenced for FOXA2 mutations and 173 primary NSCLC tumors evaluated for Foxa2 expression using an immunohistochemical assay.

resultsOut of the 25 cell lines, 13 (52%) had undetectable FOXA2 mRNA. The expression of FOXA2 mRNA and Foxa2 protein were congruent in 19/22 cells (p = 0.001). FOXA2 mutations were not identified in primary NSCLCs and were infrequent in cell lines. Focal or broad chromosomal deletions involving FOXA2 were not present. The promoter region of FOXA2 had evidence of hypermethylation, with an inverse correlation between FOXA2 mRNA expression and presence of CpG dinucleotide methylation (p < 0.0001). In primary NSCLC tumor specimens, there was a high frequency of either absence (42/173, 24.2%) or no/low expression (96/173, 55.4%) of Foxa2. In 130 patients with stage I NSCLC there was a trend towards decreased survival in tumors with no/low expression of Foxa2 (HR of 1.6, 95%CI 0.9-3.1; p = 0.122).

conclusionsLoss of expression of Foxa2 is frequent in lung cancer cell lines and NSCLCs. The main mechanism of downregulation of Foxa2 is epigenetic silencing through promoter hypermethylation. Further elucidation of the involvement of Foxa2 and other airway transcription factors in the pathogenesis of lung cancer may identify novel therapeutic targets.

Indexed as

Down-RegulationEpigenesis, GeneticAdenocarcinomaCarcinoma, Non-Small-Cell LungCell Line, TumorDNA MethylationDNA Mutational AnalysisFemaleGene DosageGene ExpressionGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-betaHumansKaplan-Meier EstimateLung NeoplasmsMaleFOXA2 protein, humanHepatocyte Nuclear Factor 3-beta

Identifiers

PMID22341411
PMCPMC3368092
OpenAlexW2167892935

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.