Evidence map›Paper›PMID 31317325›Full record

ArticleJournal of cancer research and clinical oncology2019

Loss of enhancer of zeste homologue 2 (EZH2) at tumor invasion front is correlated with higher aggressiveness in colorectal cancer cells.

Julian Böhm, Julienne Kathrin Muenzner, Aylin Caliskan, Benardina Ndreshkjana, Katharina Erlenbach-Wünsch, Susanne Merkel, Roland Croner, Tilman T Rau, Carol Immanuel Geppert, Arndt Hartmann and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  9. The association between lncRNA H19 and EZH2 expression in patients with EBV-positive laryngeal carcinoma.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2021
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  10. Review
  11. EZH2 inhibits NK cell-mediated antitumor immunity by suppressing CXCL10 expression in an HDAC10-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2021
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  14. Review
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  17. The CAM Assay as an Alternative In Vivo Model for Drug Testing.Handbook of experimental pharmacology · 2021
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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

12 authors at 3 institutions in 3 countries.

Julian BöhmExperimental Tumorpathology, Institute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstr. 22, 91054, Erlangen, Germany.
Julienne Kathrin MuenznerExperimental Tumorpathology, Institute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstr. 22, 91054, Erlangen, Germany.
Aylin CaliskanExperimental Tumorpathology, Institute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstr. 22, 91054, Erlangen, Germany.
Benardina NdreshkjanaExperimental Tumorpathology, Institute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstr. 22, 91054, Erlangen, Germany.
Katharina Erlenbach-WünschInstitute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
Susanne MerkelDepartment of Surgery, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstr. 12, 91054, Erlangen, Germany.
Roland CronerDepartment of Surgery, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstr. 12, 91054, Erlangen, Germany.
Tilman T RauInstitute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
Carol Immanuel GeppertInstitute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
Arndt HartmannInstitute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054, Erlangen, Germany.
Adriana Vial RoeheDepartment of Pathology, Federal University of Health Sciences of Porto Alegre (UFCSPA), R. Sarmento Leite, 245-Centro Histórico, Porto Alegre, RS, 90050-170, Brazil.
Regine Schneider-StockExperimental Tumorpathology, Institute of Pathology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstr. 22, 91054, Erlangen, Germany. regine.schneider-stock@uk-erlangen.de.ORCID http://orcid.org/0000-0003-0482-531X
Friedrich-Alexander-Universität Erlangen-Nürnberg · DEUniversidade Federal de Ciências da Saúde de Porto Alegre · BRUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeEnhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front.

methodsAll sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay.

resultsWe showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density.

conclusionThe differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results.

Indexed as

Margins of ExcisionAdenocarcinomaAdultAgedAged, 80 and overAnimalsBiomarkers, TumorChick EmbryoColorectal NeoplasmsDown-RegulationEnhancer of Zeste Homolog 2 ProteinFemaleHCT116 CellsHumansImmunohistochemistryMaleBiomarkers, TumorEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanCAM assayColorectal cancerEZH2EZH2 inhibitionTumor invasion frontWorse prognosis

Identifiers

PMID31317325
PMCPMC6708512
OpenAlexW2957710659

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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.