Evidence map›Paper›PMID 25927723›Full record

Trial reportBMC medical genetics2015

Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

Sushma S Thomas, Karen W Makar, Lin Li, Yingye Zheng, Peiying Yang, Lisa Levy, Rebecca Yvonne Rudolph, Paul D Lampe, Min Yan, Sanford D Markowitz and 3 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in BMC medical genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 33 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2016
    Trial
  4. Article
  5. Article
  6. Prostaglandin EImmunology · 2021
    Article
  7. Article
  8. Prostaglandin EScience advances · 2021
    Article
  9. Article
  10. Review
  11. 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

13 authors at 4 institutions in 2 countries.

Sushma S ThomasFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. ssthomas@fredhutch.org.
Karen W MakarFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. kmakar@fredhutch.org.
Lin LiFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. alex_lee001@yahoo.com.
Yingye ZhengFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. yzheng@fredhutch.org.
Peiying YangM.D. Anderson Cancer Center, Houston, TX, 77030, USA. pyang@mdanderson.org.
Lisa LevyFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. llevy@fredhutch.org.
Rebecca Yvonne RudolphFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. rrudolph7@gmail.com.
Paul D LampeFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. plampe@fredhutch.org.
Min YanCase Western Reserve University School of Medicine, Cincinnati, OH, 44106, USA. yanmin8@hotmail.com.
Sanford D MarkowitzCase Western Reserve University School of Medicine, Cincinnati, OH, 44106, USA. sxm10@case.edu.
Jeannette BiglerAmgen Corporation, Seattle, WA, 98119, USA. jbigler@amgen.com.
Johanna W LampeFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. jlampe@fredhutch.org.
John D PotterFred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. jpotter@fredhutch.org.
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZACase Western Reserve University · USAmgen (United States) · USThe University of Texas MD Anderson Cancer Center · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Targeting 15-PGDH in Colon Cancer Prognosis, Prediction, Treatment and PreventionP50CA150964 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARKOWITZ, SANFORD D. · 2011 to 2022
$24.6M
Whole Exome Approaches for Esophageal Adenocarcinoma Susceptibility GenesU54CA163060 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI CHAK, AMITABH, GUDA, KISHORE · 2011 to 2022
$14.0M
NSAID and COX/PG Metabolism and Colorectal CancerR01CA112516 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ULRICH, CORNELIA M · 2005 to 2009
$3.6M
Aspirin, UGT1A6 Genotype, and Colon Gene ExpressionR01CA094954 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI LAMPE, JOHANNA W · 2002 to 2006
$3.4M
NCATS NIH HHS UL1 TR000439NCI NIH HHS P30 CA015704NCI NIH HHS P50 CA150964NCI NIH HHS R01 CA094954NCI NIH HHS R01 CA112516NCI NIH HHS U54 CA163060
6 · The paper itself

Abstract

backgroundRegular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia.

methodsIn a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels.

resultsNo statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, but tissue PGE2 levels were lower with aspirin compared to placebo (p <0.001). Transcripts differentially expressed between epithelium and stroma (N = 4916, P <0.01, false discovery rate <0.001), included a high proportion of genes involved in cell signaling, cellular movement, and cancer. Genes preferentially expressed in epithelium were involved in drug and xenobiotic metabolism, fatty acid and lipid metabolism, apoptosis signaling, and ion transport. Genes preferentially expressed in stroma included those involved in inflammation, cellular adhesion, and extracellular matrix production. Wnt-Tcf4 pathway genes were expressed in both epithelium and stroma but differed by subcellular location.

conclusionsThese results suggest that, in healthy individuals, subtle effects of aspirin on gene expression in normal colon tissue are likely overwhelmed by inter-individual variability in microarray analyses. Differential expression of critical genes between colonic epithelium and stroma suggest that these tissue types need to be considered separately.

Indexed as

Healthy VolunteersAdultAspirinBiological TransportCell AdhesionCellular MicroenvironmentColonDinoprostoneExtracellular MatrixFemaleGene Expression RegulationGenotypeGlucuronosyltransferaseHumansIntestinal MucosaMaleAspirinDinoprostoneGlucuronosyltransferasePharmaceutical PreparationsUDP-glucuronosyltransferase, UGT1A6Xenobiotics

Identifiers

PMID25927723
PMCPMC4422425
OpenAlexW2016300450

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.