Evidence map›Paper›PMID 25545378›Full record

ArticleInflammatory bowel diseases2015

Validation of gene expression biomarker analysis for biopsy-based clinical trials in Crohn's disease.

Brigid S Boland, David L Boyle, William J Sandborn, Gary S Firestein, Barrett G Levesque, Joshua Hillman, Bing Zhang, James Proudfoot, Lars Eckmann, Peter B Ernst and 5 more

Open access · greenAbstract readComparative StudyValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammatory bowel diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Observational
  4. Observational
  5. 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 3 institutions in 2 countries.

Brigid S Boland*Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California; †San Diego Digestive Disease Research Center, University of California San Diego, La Jolla, California; ‡Department of Medicine, Division of Gastroenterology, University of California San Diego, La Jolla, California; §Clinical and Translational Research Institute, University of California San Diego, La Jolla, California; ‖Department of Medicine, Division of Rheumatology, University of California San Diego, La Jolla, California; ¶Department of Pathology, University of California San Diego, La Jolla, California; **Division of Gastroenterology & Hepatology, Kaiser Permanente, San Diego, California; and ††Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
David L Boyle
William J Sandborn
Gary S Firestein
Barrett G Levesque
Joshua Hillman
Bing Zhang
James Proudfoot
Lars Eckmann
Peter B Ernst
Jesus Rivera-Nieves
Suresh Pola
Nedret Copur-Dahi
Guangyong Zou
John T Chang
University of California, San Diego · USKaiser Permanente San Diego Medical Center · USWestern University · CA

Funding

San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
Training Grant in GastroenterologyT32DK007202 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 1985 to 2022
$7.7M
The UCSD Digestive Diseases Research Development CenterR24DK080506 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ECKMANN, LARS · 2008 to 2012
$2.7M
Regulation and Function of Polarity and Asymmetric Cell Division in ImmunityR01AI095277 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, JOHN T · 2012 to 2016
$2.6M
Understanding the Basis for Cellular Diversity During Adaptive ImmunityDP2OD008469 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, JOHN T · 2011 to 2011
$2.3M
Role of atypical Protein Kinase C in Inflammatory Bowel DiseaseR01DK093507 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, JOHN T · 2012 to 2016
$1.7M
San Diego Clinical and Translational Research InstituteTL1RR031979 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2010 to 2011
$885k
Asymmetric T cell division initiating adaptive immunity and colitisK08DK080949 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI CHANG, JOHN T · 2008 to 2012
$723k
NCATS NIH HHS UL1 TR000100NCATS NIH HHS UL1TR000100NCRR NIH HHS 1TL1RR03197NCRR NIH HHS TL1 RR031979NIAID NIH HHS R01 AI095277NIDDK NIH HHS DK080506NIDDK NIH HHS DK093507NIDDK NIH HHS K08 DK080949NIDDK NIH HHS R01 DK093507NIDDK NIH HHS R24 DK080506NIDDK NIH HHS T32 DK007202NIH HHS DP2 OD008469
6 · The paper itself

Abstract

backgroundThe ability to measure the expression of proinflammatory cytokines from intestinal biopsies in patients with Crohn's disease in an accurate and reproducible way is critical for proof-of-concept and mechanism-of-action trials; however, the number of biopsies from a segment of the ileum or colon required to yield reproducible results has not been rigorously evaluated. We examined intestinal biopsies from patients with Crohn's disease to validate methods for detecting changes in inflammatory gene expression.

methodsTo evaluate the reproducibility of gene expression measurements, intestinal biopsies were obtained from designated segments from 6 healthy controls, 6 patients with active Crohn's disease, and 6 patients with inactive Crohn's disease. Disease activity was based on the simple endoscopic score for Crohn's disease. Expression of 7 proinflammatory genes was measured from each biopsy using quantitative polymerase chain reaction. Using a linear mixed effects model, the power to detect transcriptional changes corresponding to active and inactive Crohn's disease was calculated.

resultsTotal simple endoscopic score for Crohn's disease score corresponds with expression of most inflammatory biomarkers. For most genes, 2 to 5 biopsies are needed to reduce sampling error to <25% for most genes. To measure changes in mRNA expression corresponding to active versus inactive Crohn's disease, 1 to 2 intestinal biopsies from 3 patients before and after treatment are needed to yield power of at least 80%.

conclusionsMeasuring proinflammatory gene expression from mucosal biopsies from patients with Crohn's disease is practicable and provides objective biomarkers that can be used in proof-of-concept and mechanism-of-action trials to assess response to therapy.

Indexed as

Clinical Trials as TopicAdultBiomarkersBiopsyCase-Control StudiesCohort StudiesCrohn DiseaseFemaleGene Expression ProfilingHumansIntestinal MucosaMaleMiddle AgedOligonucleotide Array Sequence AnalysisReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionBiomarkersRNA, Messenger

Identifiers

PMID25545378
PMCPMC4404151
OpenAlexW2057068760

What OpenQuestion holds

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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.