Evidence map›Paper›PMID 25217476›Full record

ArticleThorax2015

Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis.

Daryle J DePianto, Sanjay Chandriani, Alexander R Abbas, Guiquan Jia, Elsa N N'Diaye, Patrick Caplazi, Steven E Kauder, Sabyasachi Biswas, Satyajit K Karnik, Connie Ha and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Thorax, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed, 2 pooled it
14.5field-weighted citation impact, top 1% 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

167 citing papers in PubMed, 2 syntheses or guidelines pooled it, 301 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Integrated Bioinformatics and Experimental Validation to Identify Shared Sialylation-Related Signatures in Emphysematous and Fibrotic Lung Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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107 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Daryle J DePiantoGenentech Research and Early Development, South San Francisco, California, USA.
Sanjay ChandrianiGenentech Research and Early Development, South San Francisco, California, USA Novartis Institutes for Biomedical Research, Emeryville, California, USA.
Alexander R AbbasGenentech Research and Early Development, South San Francisco, California, USA.
Guiquan JiaGenentech Research and Early Development, South San Francisco, California, USA.
Elsa N N'DiayeGenentech Research and Early Development, South San Francisco, California, USA.
Patrick CaplaziGenentech Research and Early Development, South San Francisco, California, USA.
Steven E KauderGenentech Research and Early Development, South San Francisco, California, USA.
Sabyasachi BiswasGenentech Research and Early Development, South San Francisco, California, USA.
Satyajit K KarnikGenentech Research and Early Development, South San Francisco, California, USA Gilead Sciences, Foster City, California, USA.
Connie HaGenentech Research and Early Development, South San Francisco, California, USA.
Zora ModrusanGenentech Research and Early Development, South San Francisco, California, USA.
Michael A MatthayDepartment of Medicine, University of California, San Francisco, California, USA.
Jasleen KukrejaDepartment of Surgery, University of California, San Francisco, California, USA.
Harold R CollardDepartment of Medicine, University of California, San Francisco, California, USA.
Jackson G EgenGenentech Research and Early Development, South San Francisco, California, USA.
Paul J WoltersDepartment of Medicine, University of California, San Francisco, California, USA.
Joseph R ArronGenentech Research and Early Development, South San Francisco, California, USA.
University of California, San Francisco · USGilead Sciences (United States) · USNovartis (United States) · US

Funding

Targeting Epithelial Cells To Treat Pulmonary FibrosisP01HL108794 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PAPA, FEROZ R · 2012 to 2016
$12.6M
NHLBI NIH HHS HL 108794NHLBI NIH HHS P01 HL108794
6 · The paper itself

Abstract

backgroundThere is microscopic spatial and temporal heterogeneity of pathological changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We assessed relationships between gene expression patterns, pathological features, and systemic biomarkers to identify biomarkers that reflect the aggregate disease burden in patients with IPF.

methodsGene expression microarrays (N=40 IPF; 8 controls) and immunohistochemical analyses (N=22 IPF; 8 controls) of lung biopsies. Clinical characterisation and blood biomarker levels of MMP3 and CXCL13 in a separate cohort of patients with IPF (N=80).

results2940 genes were significantly differentially expressed between IPF and control samples (|fold change| >1.5, p<0.05). Two clusters of co-regulated genes related to bronchiolar epithelium or lymphoid aggregates exhibited substantial heterogeneity within the IPF population. Gene expression in bronchiolar and lymphoid clusters corresponded to the extent of bronchiolisation and lymphoid aggregates determined by immunohistochemistry in adjacent tissue sections. Elevated serum levels of MMP3, encoded in the bronchiolar cluster, and CXCL13, encoded in the lymphoid cluster, corresponded to disease severity and shortened survival time (p<10(-7) for MMP3 and p<10(-5) for CXCL13; Cox proportional hazards model).

conclusionsMicroscopic pathological heterogeneity in IPF lung tissue corresponds to specific gene expression patterns related to bronchiolisation and lymphoid aggregates. MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF.

Indexed as

Gene Expression RegulationAgedAged, 80 and overB-LymphocytesChemokine CXCL13Disease ProgressionFemaleGene Expression ProfilingHumansIdiopathic Pulmonary FibrosisImmunohistochemistryLungMaleMatrix Metalloproteinase 3Middle AgedPrognosisChemokine CXCL13CXCL13 protein, humanMatrix Metalloproteinase 3MMP3 protein, humanIdiopathic pulmonary fibrosis

Identifiers

PMID25217476
PMCPMC4472447
OpenAlexW2131492414

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.