Evidence map›Paper›PMID 24400091›Full record

ArticlePloS one2014

Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs.

Inga Hinrichsen, Matthias Kemp, Jan Peveling-Oberhag, Sandra Passmann, Guido Plotz, Stefan Zeuzem, Angela Brieger

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

Article in PloS one, 2014. 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
1.7field-weighted citation impact, top 16% 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, 38 citations in OpenAlex.

  1. Pooled it
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  14. Epigenetic heterogeneity in cancer.Biomarker research · 2019
    Review
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  17. Oncotarget · 2017
    Article
  18. Review
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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

7 authors at 1 institution in 1 country.

Inga HinrichsenMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Matthias KempMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Jan Peveling-OberhagMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Sandra PassmannMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Guido PlotzMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Stefan ZeuzemMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Angela BriegerMedical Clinic I, Biomedical Research Laboratory, Goethe-University, Frankfurt a.M., Germany.
Goethe University Frankfurt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC) specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV). However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR) genes and thereby enhanced progression of hepatocarcinogenesis has been the subject of controversial discussion. We investigated promoter methylation pattern of the MMR genes MLH1, MSH2 and PMS2 as well as the cyclin-dependent kinase inhibitor 2A gene (p16) in 61 well characterized patients with HCCs associated with HCV, Hepatitis B virus infection or alcoholic liver disease. DNA was isolated from formalin-fixed, paraffin-embedded tumour and non-tumour adjacent tissue and analysed by methylation-specific PCR. Moreover, microsatellite analysis was performed in tissues showing methylation in MMR gene promoters. Our data demonstrated that promoter methylation of MLH1, MSH2, PMS2 and p16 is present among all considered HCCs. Hereby, promoter silencing was detectable more frequently in advanced-stage HCCs than in low-stage ones. However, there was no significant correlation between aberrant DNA methylation of MMR genes or p16 and HCV infection in related HCC specimens. In summary, we show that promoter methylation of essential MMR genes and p16 is detectable in HCCs most dominantly in pT3 stage tumour cases. Since loss of MMR proteins was previously described to be not only responsible for tumour development but also for chemotherapy resistance, the knowledge of mechanisms jointly responsible for HCC progression might enable significant improvement of individual HCC therapy in the future.

Indexed as

Adaptor Proteins, Signal TransducingAdenosine TriphosphatasesAdultAgedCarcinoma, HepatocellularCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDNA MethylationDNA Repair EnzymesFemaleHumansLiver NeoplasmsMaleMicrosatellite InstabilityMiddle AgedMismatch Repair Endonuclease PMS2Adaptor Proteins, Signal TransducingAdenosine TriphosphatasesCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDNA Repair EnzymesMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinNuclear ProteinsPMS2 protein, human

Identifiers

PMID24400091
PMCPMC3882222
OpenAlexW1995402091

What OpenQuestion holds

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LicenceCC BY
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.