Evidence map›Paper›PMID 32586194›Full record

ArticleMolecular pain

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain.

Kord M Kober, Man-Cheung Lee, Adam Olshen, Yvette P Conley, Marina Sirota, Michael Keiser, Marilyn J Hammer, Gary Abrams, Mark Schumacher, Jon D Levine and 1 more

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

Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 13% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
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  6. Addressing the Needs of Breast Cancer Survivors.Current oncology reports · 2025
    Review
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  11. Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024
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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

11 authors at 3 institutions in 1 country.

Kord M KoberSchool of Nursing, University of California, San Francisco, CA, USA.ORCID 0000-0001-9732-3321
Man-Cheung LeeSchool of Medicine, University of California, San Francisco, CA, USA.
Adam OlshenHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Yvette P ConleySchool of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.
Marina SirotaBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
Michael KeiserBakar Computational Health Sciences Institute, University of California, San Francisco, CA, USA.
Marilyn J HammerPhyllis F. Cantor Center, Dana-Farber Cancer Institute, Boston, MA, USA.
Gary AbramsSchool of Medicine, University of California, San Francisco, CA, USA.
Mark SchumacherSchool of Medicine, University of California, San Francisco, CA, USA.
Jon D LevineSchool of Medicine, University of California, San Francisco, CA, USA.
Christine MiaskowskiSchool of Nursing, University of California, San Francisco, CA, USA.
University of California, San Francisco · USDana-Farber Cancer Institute · USUniversity of Pittsburgh · US

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
Characterization of and Treatment for Chemotherapy NeuropathyR01CA151692 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MIASKOWSKI, CHRISTINE A. · 2011 to 2015
$6.4M
Advancing the Science of Symptom Management in Oncology PatientsK05CA168960 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MIASKOWSKI, CHRISTINE A. · 2013 to 2017
$453k
NCATS NIH HHS UL1 TR000004NCI NIH HHS K05 CA168960NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA151692
6 · The paper itself

Abstract

backgroundPaclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life. No interventions are available to treat PIPN. In our previous studies, we identified that the HIF-1 signaling pathway (H1SP) was perturbed between breast cancer survivors with and without PIPN. Preclinical studies suggest that the H1SP is involved in the development of bortezomib-induced and diabetic peripheral neuropathy, and sciatic nerve injury. The purpose of this study was to identify H1SP genes that have both differential methylation and differential gene expression between breast cancer survivors with and without PIPN.

methodsA multi-staged integrated analysis was performed. In peripheral blood, methylation was assayed using microarray and gene expression was assayed using RNA-seq. Candidate genes in the H1SP having both differentially methylation and differential expression were identified between survivors who received paclitaxel and did (n = 25) and did not (n = 25) develop PIPN. Then, candidate genes were evaluated for differential methylation and differential expression in public data sets of preclinical models of PIPN and sciatic nerve injury.

resultsEight candidate genes were identified as both differential methylation and differential expression in survivors. Of the eight homologs identified, one was found to be differential expression in both PIPN and "normal" mice dorsal root ganglia; three were differential methylation in sciatic nerve injury versus sham rats in both pre-frontal cortex and T-cells; and two were differential methylation in sciatic nerve injury versus sham rats in the pre-frontal cortex.

conclusionsThis study is the first to evaluate for methylation in cancer survivors with chronic PIPN. The findings provide evidence that the expression of H1SP genes associated with chronic PIPN in cancer survivors may be regulated by epigenetic mechanisms and suggests genes for validation as potential therapeutic targets.

Indexed as

Cancer SurvivorsGene Expression RegulationSignal TransductionAnimalsBreast NeoplasmsDisease Models, AnimalDNA MethylationFemaleGene Expression ProfilingHumansHypoxia-Inducible Factor 1NeuralgiaPaclitaxelPeripheral Nerve InjuriesPrefrontal CortexPromoter Regions, GeneticHypoxia-Inducible Factor 1Paclitaxelbreast cancerchemotherapygene expressionhypoxia-inducible factorintegrated genomic analysismethylationPaclitaxel-induced peripheral neuropathysurvivor

Identifiers

PMID32586194
PMCPMC7322824
OpenAlexW3037150880

What OpenQuestion holds

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LicenceCC BY-NC
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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.