Evidence map›Paper›PMID 27272216›Full record

ArticleBritish journal of cancer2016

Association of CpG island methylator phenotype and EREG/AREG methylation and expression in colorectal cancer.

Michael S Lee, Elizabeth J McGuffey, Jeffrey S Morris, Ganiraju Manyam, Veerabahdran Baladandayuthapani, Wei Wei, Van K Morris, Michael J Overman, Dipen M Maru, Zhi-Qin Jiang and 2 more

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

Article in British journal of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 4 pooled it
7.9field-weighted citation impact, top 2% 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

61 citing papers in PubMed, 4 syntheses or guidelines pooled it, 99 citations in OpenAlex.

  1. Pooled it
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  11. Current Status of Precision Medicine in Colorectal Cancer in Japan.International journal of molecular sciences · 2025
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1 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 1 country.

Michael S LeeDivision of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive, CB 7305, Chapel Hill, NC 27599, USA.
Elizabeth J McGuffeyUnited States Naval Academy, Department of Mathematics, 572C Holloway Road, Annapolis, MD 21402, USA.
Jeffrey S MorrisDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Ganiraju ManyamDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Veerabahdran BaladandayuthapaniDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Wei WeiDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Van K MorrisDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Michael J OvermanDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Dipen M MaruDepartment of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Zhi-Qin JiangDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Stanley R HamiltonDepartment of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Scott KopetzDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
The University of Texas MD Anderson Cancer Center · USUnited States Naval Academy · USUniversity of North Carolina at Chapel Hill · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Tumor Heterogeneity and Acquired Resistance to EGFR InhibitionR01CA184843 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAMILTON, STANLEY R., KOPETZ, SCOTT · 2015 to 2019
$3.2M
Bayesian methods for complex, high-dimensional functional data in cancer researchR01CA178744 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MORRIS, JEFFREY S · 2015 to 2019
$1.7M
Stress Signaling Pathways and Resistance in Colorectal CancerR01CA172670 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT · 2013 to 2017
$1.6M
Integrative methods for high-dimensional genomics dataR01CA160736 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BALADANDAYUTHAPANI, VEERABHADRAN · 2011 to 2014
$1.4M
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA160736NCI NIH HHS R01 CA172670NCI NIH HHS R01 CA178744NCI NIH HHS R01 CA184843
6 · The paper itself

Abstract

backgroundHigh EREG and AREG expression, and left-sided primary tumours are associated with superior efficacy of anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (CRC), but a unifying explanation of these findings is lacking.

methodsRNA-seq, gene expression arrays, and DNA methylation profiling were completed on 179 CRC tumours. Results were validated using independent The Cancer Genome Atlas data sets. An independent cohort of 198 KRAS wild-type metastatic CRC tumours was tested for CpG island methylator phenotype (CIMP) status, and progression-free survival (PFS) with the first anti-EGFR regimen was retrospectively determined.

resultsEREG and AREG expression was highly inversely correlated with methylation and was inversely associated with right-sided primary tumour, BRAF mutation, and CIMP-high status. Treatment of CRC cell lines with hypomethylating agents decreased methylation and increased expression of EREG. Inferior PFS with anti-EGFR therapy was associated with CIMP-high status, BRAF mutation, NRAS mutation, and right-sided primary tumour on univariate analysis. Among known BRAF/NRAS wild-type tumours, inferior PFS remained associated with CIMP-high status (median PFS 5.6 vs 9.0 mo, P=0.023).

conclusionsEREG and AREG are strongly regulated by methylation, and their expression is associated with CIMP status and primary tumour site, which may explain the association of primary tumour site and EREG/AREG expression with anti-EGFR therapy efficacy.

Indexed as

CpG IslandsDNA MethylationAmphiregulinCohort StudiesColorectal NeoplasmsEpiregulinErbB ReceptorsHCT116 CellsHumansMalePhenotypePromoter Regions, GeneticProto-Oncogene Proteins p21(ras)AmphiregulinAREG protein, humanEGFR protein, humanEpiregulinErbB ReceptorsEREG protein, humanKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID27272216
PMCPMC4984478
OpenAlexW2411708874

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.