Evidence map›Paper›PMID 29732557›Full record

ArticleThe Journal of pathology2018

Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target.

Jinfeng Cao, Kelly Cs Pontes, Renier C Heijkants, Niels J Brouwer, Arwin Groenewoud, Ekaterina S Jordanova, Marina Marinkovic, Sjoerd van Duinen, Amina Fas Teunisse, Robert M Verdijk and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Diabetic keratopathy and nuclear proteins (Review).Molecular medicine reports · 2026
    Review
  3. Review
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  5. Review
  6. Review
  7. Article
  8. Epigenetics in the Diagnosis and Therapy of Malignant Melanoma.International journal of molecular sciences · 2022
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
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

13 authors at 3 institutions in 2 countries.

Jinfeng CaoDepartment of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands.ORCID 0000-0001-8826-311X
Kelly Cs PontesDepartment of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands.
Renier C HeijkantsDepartment of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Niels J BrouwerDepartment of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands.
Arwin GroenewoudDepartment of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
Ekaterina S JordanovaDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Marina MarinkovicDepartment of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands.
Sjoerd van DuinenDepartment of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Amina Fas TeunisseDepartment of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Robert M VerdijkDepartment of Pathology, Section Ophthalmic Pathology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
Ewa Snaar-JagalskaDepartment of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
Aart G JochemsenDepartment of Molecular Cell Biology, Leiden University Medical Centre, Leiden, The Netherlands.
Martine J JagerDepartment of Ophthalmology, Leiden University Medical Centre, Leiden, The Netherlands.
Leiden University Medical Center · NLLeiden University · NLErasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malignant melanoma of the conjunctiva (CM) is an uncommon but potentially deadly disorder. Many malignancies show an increased activity of the epigenetic modifier enhancer of zeste homolog 2 (EZH2). We studied whether EZH2 is expressed in CM, and whether it may be a target for therapy in this malignancy. Immunohistochemical analysis showed that EZH2 protein expression was absent in normal conjunctival melanocytes and primary acquired melanosis, while EZH2 was highly expressed in 13 (50%) of 26 primary CM and seven (88%) of eight lymph node metastases. Increased expression was positively associated with tumour thickness (p =0.03). Next, we targeted EZH2 with specific inhibitors (GSK503 and UNC1999) or depleted EZH2 by stable shRNA knockdown in three primary CM cell lines. Both pharmacological and genetic inactivation of EZH2 inhibited cell growth and colony formation and influenced EZH2-mediated gene transcription and cell cycle profile in vitro. The tumour suppressor gene p21/CDKN1A was especially upregulated in CM cells after EZH2 knockdown in CM cells. Additionally, the potency of GSK503 against CM cells was monitored in zebrafish xenografts. GSK503 profoundly attenuated tumour growth in CM xenografts at a well-tolerated concentration. Our results indicate that elevated levels of EZH2 are relevant to CM tumourigenesis and progression, and that EZH2 may become a potential therapeutic target for patients with CM. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Indexed as

AdultAgedAged, 80 and overAnimalsAntineoplastic AgentsBenzamidesCell Cycle CheckpointsCell LineCell ProliferationConjunctival NeoplasmsCyclin-Dependent Kinase Inhibitor p21Enhancer of Zeste Homolog 2 ProteinFemaleGene Expression Regulation, NeoplasticHumansIndazolesAntineoplastic AgentsBenzamidesCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21Enhancer of Zeste Homolog 2 ProteinEZH2 protein, humanIndazolesPiperazinesPyridonesRNA, Small InterferingUNC1999cell deathconjunctival melanomaEZH2histone methylationprimary acquired melanosiszebrafish

Identifiers

PMID29732557
PMCPMC6174981
OpenAlexW2802052026

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.