Evidence map›Paper›PMID 25203737›Full record

ArticlePharmacogenetics and genomics2014

Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in locally advanced gastric cancer patients after surgery with curative intent.

Takeru Wakatsuki, Sebastian Stintzing, Wu Zhang, Dongyun Yang, Mizutomo Azuma, Yan Ning, Shinichi Yamauchi, Satoshi Matsusaka, Nico B Volz, Yu Sunakawa and 6 more

Abstract read
In one paragraph

Article in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact, top 75% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
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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

16 authors at 3 institutions in 2 countries.

Takeru WakatsukiaSharon Carpenter Laboratory, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, California bMemorial Sloan Kettering Cancer Center, New York, New York, USA cDepartment of Gastroenterology Center, Cancer Institute Hospital, Tokyo Departments of dGastroenterology eSurgery, School of Medicine, Kitasato University, Sagamihara, Japan fDepartment of Hematology and Oncology, University Hospital Grosshadern, University of Munich, Munich, Germany.
Sebastian Stintzing
Wu Zhang
Dongyun Yang
Mizutomo Azuma
Yan Ning
Shinichi Yamauchi
Satoshi Matsusaka
Nico B Volz
Yu Sunakawa
Wasaburo Koizumi
Masahiko Watanabe
Afsaneh Barzi
Anthony B El Khoueiry
Manish A Shah
Heinz-Josef Lenz
Kitasato University · JPMemorial Sloan Kettering Cancer Center · USUSC Norris Comprehensive Cancer Center · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
NCI NIH HHS 5P30CA014089-27S1NCI NIH HHS P30 CA014089
6 · The paper itself

Abstract

objectiveAmphiregulin (AREG) and epiregulin (EREG) are important ligands to the epithelial growth factor receptor, which is involved in the regulation of progression and stemness in gastric cancer (GC). This study investigated whether frequent single nucleotide polymorphisms (SNPs) in genes of AREG and EREG are associated with recurrence-free survival and overall survival in patients with locally advanced GC.

methodsSNPs with a minor allele frequency of at least 10% were analyzed using direct DNA sequencing in two independent study populations.

resultsThe minor allele of AREG rs1615111 was associated with a significantly higher 3-year recurrence rate and lower 3-year survival rate [hazard ratio (HR)=2.21 and 2.35, respectively] compared with patients homozygous for the dominant allele G. The value for overall survival could be validated with a HR of 2.54 (P=0.018) in an independent cohort. Patients homozygous for the minor allele A of EREG rs12641042 had a significantly higher 3-year survival rate than patients with allele C (HR 0.48; P=0.034), but significance was lost in multivariable analysis (P=0.066). The value of rs12641042 could not be validated (P=0.98). Exploratory multivariable subgroup analysis showed the strongest prognostic value for rs1615111 in tumors with a diffuse histology (Pfor interaction=0.004).

conclusionAREG rs1615111, located in the AREG genomic region, can significantly define different prognostic cohorts in locally advanced GC. This value is most evident in GC patients with diffuse histology, which might be relevant as none of the trials testing epithelial growth factor receptor inhibitors has been enriched for diffuse histology or a molecularly defined population.

Indexed as

Polymorphism, Single NucleotideAgedAmphiregulinBiomarkers, TumorCohort StudiesEGF Family of ProteinsEpiregulinFemaleHumansMalePrognosisStomach NeoplasmsAmphiregulinAREG protein, humanBiomarkers, TumorEGF Family of ProteinsEpiregulinEREG protein, human

Identifiers

PMID25203737
PMCPMC4190127
OpenAlexW2319897135

What OpenQuestion holds

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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.