Evidence map›Paper›PMID 21325429›Full record

ArticleCancer research2011

Modulation of cystatin A expression in human airway epithelium related to genotype, smoking, COPD, and lung cancer.

Marcus W Butler, Tomoya Fukui, Jacqueline Salit, Renat Shaykhiev, Jason G Mezey, Neil R Hackett, Ronald G Crystal

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
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  5. Heliyon · 2025
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  20. Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2013
    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

7 authors at 1 institution in 1 country.

Marcus W ButlerDepartment of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
Tomoya Fukui
Jacqueline Salit
Renat Shaykhiev
Jason G Mezey
Neil R Hackett
Ronald G Crystal
Cornell University · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024996 · NCRR · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 2007 to 2011
$49.6M
Role of Alveolar Macrophages in the Accelerated Emphysema of HIV-1 PositiveP50HL084936 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CRYSTAL, RONALD G · 2007 to 2011
$14.2M
Candidate Genes for Susceptibility to BronchitisR01HL074326 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CRYSTAL, RONALD G · 2004 to 2007
$2.4M
NCRR NIH HHS UL1 RR024996NCRR NIH HHS UL1-RR024996.NHLBI NIH HHS P50 HL084936NHLBI NIH HHS R01 HL074326
6 · The paper itself

Abstract

The cathepsin inhibitor Cystatin A (CSTA) has antiapoptotic properties linked with neoplastic changes in squamous cell epithelium, where it has been proposed as a diagnostic and prognostic marker of lung cancer. Notably, cystatin A is upregulated in dysplastic epithelium, prompting us to hypothesize that it might be modulated in chronic obstructive pulmonary disease (COPD), a small airway epithelial (SAE) disorder that is a risk factor for non-small cell lung cancer (NSCLC) in a subset of smokers. Here we report that genetic variation, smoking, and COPD can all elevate levels of CSTA expression in lung small airway epithelia, with still further upregulation in squamous cell carcinoma (SCC), an NSCLC subtype. We examined SAE gene expression in 178 individuals, including healthy nonsmokers (n = 60), healthy smokers (n = 82), and COPD smokers (n = 36), with corresponding large airway epithelium (LAE) data included in a subset of subjects (n = 52). Blood DNA was genotyped by SNP microarray. Twelve SNPs upstream of the CSTA gene were found to associate with its expression in SAE. Levels were higher in COPD smokers than in healthy smokers, who, in turn, had higher levels than nonsmokers. CSTA gene expression in LAE was also smoking-responsive. Using publicly available NSCLC expression data we also found that CSTA was upregulated in SCC versus LAE and downregulated in adenocarcinoma versus smoke-exposed SAE. All phenotypes were associated with different proportional expression of CSTA to cathepsins. Our findings establish that genetic variability, smoking, and COPD all influence CSTA expression, as does SCC, supporting the concept that CSTA may make pivotal contributions to NSCLC pathogenesis in both early and late stages of disease development.

Indexed as

AdenocarcinomaAdenocarcinoma of LungCarcinoma, Squamous CellCystatin AGene ExpressionGenotypeHumansLung NeoplasmsPolymorphism, Single NucleotidePulmonary Disease, Chronic ObstructiveRespiratory MucosaSmokingCSTA protein, humanCystatin A

Identifiers

PMID21325429
PMCPMC3209453
OpenAlexW2099156318

What OpenQuestion holds

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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.