Evidence map›Paper›PMID 24483146›Full record

ArticleBMC genomics2014

Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines.

Liang Li, Brooke L Fridley, Krishna Kalari, Nifang Niu, Gregory Jenkins, Anthony Batzler, Ryan P Abo, Daniel Schaid, Liewei Wang

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.3field-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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  4. Impaired Blastocyst Formation inInternational journal of molecular sciences · 2023
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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

9 authors at 2 institutions in 1 country.

Liang Li
Brooke L Fridley
Krishna Kalari
Nifang Niu
Gregory Jenkins
Anthony Batzler
Ryan P Abo
Daniel Schaid
Liewei WangDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. wang.liewei@mayo.edu.
Mayo Clinic in Florida · USMayo Clinic · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
Tissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI PETERSEN, GLORIA M. · 2004 to 2018
$32.7M
Pharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8M
Pharmacogenomics and Mechanisms of Cytidine AnaloguesR01CA138461 · NCI · MAYO CLINIC ROCHESTER · PI WANG, LIEWEI · 2009 to 2013
$1.5M
Pharmacogenomics of a Cytidine Analogue, GemcitabineK22CA130828 · NCI · MAYO CLINIC ROCHESTER · PI WANG, LIEWEI · 2008 to 2010
$492k
NCI NIH HHS K22 CA130828NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA102701NCI NIH HHS R01 CA138461NIGMS NIH HHS U19 GM61388
6 · The paper itself

Abstract

backgroundTwo cytidine analogues, gemcitabine and cytosine arabinoside (AraC), are widely used in the treatment of a variety of cancers with a large individual variation in response. To identify potential genetic biomarkers associated with response to these two drugs, we used a human lymphoblastoid cell line (LCL) model system with extensive genomic data, including 1.3 million SNPs and 54,000 basal expression probesets to perform genome-wide association studies (GWAS) with gemcitabine and AraC IC50 values.

resultsWe identified 11 and 27 SNP loci significantly associated with gemcitabine and AraC IC50 values, respectively. Eleven candidate genes were functionally validated using siRNA knockdown approach in multiple cancer cell lines. We also characterized the potential mechanisms of genes by determining their influence on the activity of 10 cancer-related signaling pathways using reporter gene assays. Most SNPs regulated gene expression in a trans manner, except 7 SNPs in the PIGB gene that were significantly associated with both the expression of PIGB and gemcitabine cytotoxicity.

conclusionThese results suggest that genetic variation might contribute to drug response via either cis- or trans- regulation of gene expression. GWAS analysis followed by functional pharmacogenomics studies might help identify novel biomarkers contributing to variation in response to these two drugs and enhance our understanding of underlying mechanisms of drug action.

Indexed as

ApoptosisCell Line, TumorCytarabineDeoxycytidineGemcitabineGenetic MarkersGenome-Wide Association StudyGenotypeHumansLinkage DisequilibriumMannosyltransferasesPolymorphism, Single NucleotideRegulatory Elements, TranscriptionalRNA InterferenceRNA, Small InterferingCytarabineDeoxycytidineGemcitabineGenetic MarkersMannosyltransferasesPIGB protein, humanRNA, Small Interfering

Identifiers

PMID24483146
PMCPMC3930546
OpenAlexW2002376494

What OpenQuestion holds

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LicenceCC BY
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.