Evidence map›Paper›PMID 27379752›Full record

ArticleEpigenetics2016

RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis.

M J A M Clausen, L J Melchers, M F Mastik, L Slagter-Menkema, H J M Groen, B F A M van der Laan, W van Criekinge, T de Meyer, S Denil, B van der Vegt and 3 more

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

Article in Epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Observational
  5. Article
  6. The Endosomal Recycling Pathway-At the Crossroads of the Cell.International journal of molecular sciences · 2020
    Review
  7. Article
  8. Wnt/β-Catenin Signaling in Oral Carcinogenesis.International journal of molecular sciences · 2020
    Review
  9. Article
  10. Article
  11. Article
  12. 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.

M J A M Clausena Departments of Pathology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
L J Melchersa Departments of Pathology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
M F Mastika Departments of Pathology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
L Slagter-Menkemaa Departments of Pathology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
H J M Groend Pulmonary Diseases, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
B F A M van der Laanc Otorhinolaryngology/Head & Neck Surgery, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
W van Criekingee Department of Mathematical Modeling , Statistics and Bioinformatics, Ghent University , Ghent , Belgium.
T de Meyere Department of Mathematical Modeling , Statistics and Bioinformatics, Ghent University , Ghent , Belgium.
S Denilf Gynecologic Oncology, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
B van der Vegta Departments of Pathology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
G B A Wismanf Gynecologic Oncology, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
J L N Roodenburgb Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
E Schuuringa Departments of Pathology , University of Groningen, University Medical Center Groningen , Groningen , the Netherlands.
University of Groningen · NLUniversity Medical Center Groningen · NLGhent University · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Oral and oropharyngeal squamous cell carcinoma (OOSCC) have a low survival rate, mainly due to metastasis to the regional lymph nodes. For optimal treatment of these metastases, a neck dissection is required; however, inaccurate detection methods results in under- and over-treatment. New DNA prognostic methylation biomarkers might improve lymph node metastases detection. To identify epigenetically regulated genes associated with lymph node metastases, genome-wide methylation analysis was performed on 6 OOSCC with (pN+) and 6 OOSCC without (pN0) lymph node metastases and combined with a gene expression signature predictive for pN+ status in OOSCC. Selected genes were validated using an independent OOSCC cohort by immunohistochemistry and pyrosequencing, and on data retrieved from The Cancer Genome Atlas. A two-step statistical selection of differentially methylated sequences revealed 14 genes with increased methylation status and mRNA downregulation in pN+ OOSCC. RAB25, a known tumor suppressor gene, was the highest-ranking gene in the discovery set. In the validation sets, both RAB25 mRNA (P = 0.015) and protein levels (P = 0.012) were lower in pN+ OOSCC. RAB25 mRNA levels were negatively correlated with RAB25 methylation levels (P < 0.001) but RAB25 protein expression was not. Our data revealed that promoter methylation is a mechanism resulting in downregulation of RAB25 expression in pN+ OOSCC and decreased expression is associated with lymph node metastasis. Detection of RAB25 methylation might contribute to lymph node metastasis diagnosis and serve as a potential new therapeutic target in OOSCC.

Indexed as

Down-RegulationEpigenesis, GeneticAdolescentAdultAgedAged, 80 and overCarcinoma, Squamous CellDNA MethylationFemaleHumansLymphatic MetastasisMaleMiddle AgedOropharyngeal NeoplasmsPromoter Regions, Geneticrab GTP-Binding ProteinsRab25 protein, humanrab GTP-Binding ProteinsRNA, MessengerDNA methylationepigenetic regulationhead and neck cancermetastasisMethylCap-Seqoral squamous cell carcinoma

Identifiers

PMID27379752
PMCPMC5048719
OpenAlexW2472718921

What OpenQuestion holds

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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.