Evidence map›Paper›PMID 30257705›Full record

ArticleClinical epigenetics2018

CDX2 in colorectal cancer is an independent prognostic factor and regulated by promoter methylation and histone deacetylation in tumors of the serrated pathway.

Janina Graule, Kristin Uth, Elia Fischer, Irene Centeno, José A Galván, Micha Eichmann, Tilman T Rau, Rupert Langer, Heather Dawson, Ulrich Nitsche and 9 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
8.0field-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

43 citing papers in PubMed, 87 citations in OpenAlex.

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  19. Loss ofEcancermedicalscience · 2024
    Article
  20. Novel inheritedCold Spring Harbor molecular case studies · 2023
    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

19 authors at 4 institutions in 3 countries.

Janina GrauleInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Kristin UthInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Elia FischerInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Irene CentenoInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
José A GalvánInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Micha EichmannInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Tilman T RauInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Rupert LangerInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Heather DawsonInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Ulrich NitscheDepartment of Surgery, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, Munich, 81675, Germany.
Peter TraegerCareanesth AG, Nelkenstrasse 15, Zürich, 8006, Switzerland.
Martin D BergerDepartment of Medical Oncology, University Hospital of Bern, 3010, Bern, Switzerland.
Beat SchnürigerDepartment of Visceral and Internal Medicine, University Hospital of Bern, 3008, Bern, Switzerland.
Marion HädrichDepartment of Visceral and Internal Medicine, University Hospital of Bern, 3008, Bern, Switzerland.
Peter StuderDepartment of Visceral and Internal Medicine, University Hospital of Bern, 3008, Bern, Switzerland.
Daniel InderbitzinUniversity of Bern and Bürgerspital Solothurn, Schöngrünstrasse 42, 4500, Solothurn, Switzerland.
Alessandro LugliInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Mario P TschanInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland.
Inti ZlobecInstitute of Pathology, University of Bern, Murtenstrasse 31, Room L310, 3008, Bern, Switzerland. inti.zlobec@pathology.unibe.ch.ORCID 0000-0001-6741-3000
University of Bern · CHUniversity Hospital of Bern · CHTUM Klinikum · DEUniversity of Southern California · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn colorectal cancer, CDX2 expression is lost in approximately 20% of cases and associated with poor outcome. Here, we aim to validate the clinical impact of CDX2 and investigate the role of promoter methylation and histone deacetylation in CDX2 repression and restoration.

methodsCDX2 immunohistochemistry was performed on multi-punch tissue microarrays (n = 637 patients). Promoter methylation and protein expression investigated on 11 colorectal cancer cell lines identified two CDX2 low expressors (SW620, COLO205) for treatment with decitabine (DNA methyltransferase inhibitor), trichostatin A (TSA) (general HDAC inhibitor), and LMK-235 (specific HDAC4 and HDAC5 inhibitor). RNA and protein levels were assessed. HDAC5 recruitment to the CDX2 gene promoter region was tested by chromatin immunoprecipitation.

resultsSixty percent of tumors showed focal CDX2 loss; 5% were negative. Reduced CDX2 was associated with lymph node metastasis (p = 0.0167), distant metastasis (p = 0.0123), and unfavorable survival (multivariate analysis: p = 0.0008; HR (95%CI) 0.922 (0.988-0.997)) as well as BRAF

conclusionCDX2 loss is an adverse prognostic factor and linked to molecular features of the serrated pathway. RNA/protein expression is restored in CDX2 low-expressing CRC cell lines by demethylation and HDAC inhibition. Importantly, our data underline HDAC4 and HDAC5 as new epigenetic CDX2 regulators that warrant further investigation.

Indexed as

DNA MethylationBenzamidesCaco-2 CellsCDX2 Transcription FactorCell Line, TumorColorectal NeoplasmsCpG IslandsDecitabineFemaleGene Expression Regulation, NeoplasticHCT116 CellsHistonesHT29 CellsHumansHydroxamic AcidsMaleBenzamidesCDX2 protein, humanCDX2 Transcription FactorDecitabineHistonesHydroxamic AcidsLMK-235trichostatin ABiomarkerCDX2Colorectal cancerHistone modificationMethylationPrognosis

Identifiers

PMID30257705
PMCPMC6158822
OpenAlexW2893530958

What OpenQuestion holds

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LicenceCC BY
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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.