Evidence map›Paper›PMID 26553291›Full record

ArticleBMC cancer2015

Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer.

Lorenzo Fornaro, Pinuccia Faviana, Veronica De Gregorio, Caterina Vivaldi, Elisa Paolicchi, Gianluca Masi, Fotios Loupakis, Elisa Sensi, Cristiana Lupi, Gabriella Fontanini and 4 more

Abstract read
In one paragraph

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
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

14 authors.

Lorenzo FornaroUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. lorenzo.fornaro@gmail.com.
Pinuccia FavianaUnit of Pathology, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy. pinuccia.faviana@med.unipi.it.
Veronica De GregorioUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. veronicadegregorio@libero.it.
Caterina VivaldiUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. caterinavivaldi@gmail.com.
Elisa PaolicchiDepartment of Biology, Unit of Genetics, University of Pisa, Pisa, Italy. eli.paolicchi@gmail.com.
Gianluca MasiUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. gl.masi@tin.it.
Fotios LoupakisUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. fotiosloupakis@gmail.com.
Elisa SensiUnit of Pathology, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy. e.sensi@med.unipi.it.
Cristiana LupiUnit of Pathology, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy. cristianalupi@libero.it.
Gabriella FontaniniUnit of Pathology, Department of Surgical, Medical and Molecular Pathology and Critical Care, University of Pisa, Pisa, Italy. gabriella.fontanini@med.unipi.it.
Yuzhuo WangExperimental Therapeutics, BCCA Cancer Research Centre, Vancouver, BC, Canada. ywang@bccrc.ca.
Romano DanesiPharmacology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. romano.danesi@med.unipi.it.
Alfredo FalconeUnit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy. alfredo.falcone@med.unipi.it.
Francesco CreaExperimental Therapeutics, BCCA Cancer Research Centre, Vancouver, BC, Canada. francesco.crea@open.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking.

methods119 primary CRCs were analyzed. SNP was evaluated by real-time PCR from colonic healthy tissue, while EZH2 and H3K27me3 expression were studied by immunohistochemistry. We primarily looked for correlation between EZH2 rs3757441 genotypes and EZH2/H3K27me3 expression. Potential associations between EZH2/H3K27me3 expression and clinico-pathological features or KRAS exon 2 and BRAF exon 15 mutations were secondary endpoints. Statistical analysis was performed by chi-square test, T-test or ANOVA.

resultsThe C/C genotype was significantly associated with higher EZH2 (100 vs. 44 %; P = 0.019) and H3K27me3 (100 vs. 38 %; P = 0.009) staining intensity compared with C/T and T/T. EZH2 3+ staining significantly correlated with stronger H3K27me3 expression (P = 0.039). KRAS and BRAF mutations were not associated with EZH2 or H3K27me3 expression.

conclusionEZH2 rs3757441 C/C genotype is associated with stronger EZH2 and H3K27me3 immunoreactivity in primary CRC: this SNP may serve as a promising biomarker for EZH2-targeting agents and may add independent information to KRAS and BRAF testing.

Indexed as

PrognosisBiomarkers, TumorColorectal NeoplasmsEnhancer of Zeste Homolog 2 ProteinFemaleGene Expression Regulation, NeoplasticGenotypeHistonesHumansMaleMutationNeoplasm StagingPolycomb Repressive Complex 2Polymorphism, Single NucleotideProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)Biomarkers, TumorBRAF protein, humanEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanHistonesKRAS protein, humanPolycomb Repressive Complex 2Proto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)

Identifiers

PMID26553291
PMCPMC4640238

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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.