Evidence map›Paper›PMID 30081853›Full record

ArticleBMC cancer2018

TRH site-specific methylation in oral and oropharyngeal squamous cell carcinoma.

C Puttipanyalears, A Arayataweegool, K Chalertpet, P Rattanachayoto, P Mahattanasakul, N Tangjaturonsasme, V Kerekhanjanarong, A Mutirangura, N Kitkumthorn

Open access · goldAbstract readValidation Study
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
0.8field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. International journal of molecular sciences · 2025
    Article
  4. Review
  5. A Narrative Review on Oral Squamous Cell Carcinoma.Journal of pharmacy & bioallied sciences · 2025
    Review
  6. Biological biomarkers of oral cancer.Periodontology 2000 · 2024
    Review
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  8. Article
  9. Review
  10. Article
  11. Article
  12. 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

9 authors at 3 institutions in 1 country.

C PuttipanyalearsDepartment of Anatomy, Faculty of Medicine, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Chulalongkorn University, Bangkok, 10330, Thailand.
A ArayataweegoolDepartment of Anatomy, Faculty of Medicine, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Chulalongkorn University, Bangkok, 10330, Thailand.
K ChalertpetDepartment of Anatomy, Faculty of Medicine, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Chulalongkorn University, Bangkok, 10330, Thailand.
P RattanachayotoDivision of Medical Oncology, Department of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
P MahattanasakulDepartment of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Pathumwa, Bangkok, 10330, Thailand.
N TangjaturonsasmeDepartment of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Pathumwa, Bangkok, 10330, Thailand.
V KerekhanjanarongDepartment of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, Chulalongkorn University, Pathumwa, Bangkok, 10330, Thailand.
A MutiranguraDepartment of Anatomy, Faculty of Medicine, Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Chulalongkorn University, Bangkok, 10330, Thailand.
N KitkumthornDepartment of Oral Biology, Faculty of Dentistry, Mahidol University, 6 Yothi Road, Ratchathewi, Bangkok, 10400, Thailand. nakarinkit@gmail.com.
Chulalongkorn University · THKing Chulalongkorn Memorial Hospital · THMahidol University · TH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe incidence of oral squamous cell carcinoma (OSCC) continues to increase each year. Clinical examination and biopsy usually detect OSCC at an advanced stage that is difficult to treat, leading to poor prognosis. DNA methylation pattern is tissue specific and has emerged as a biomarker for the detection of cancers of tissue origin. Herein, we aimed to discover a novel site-specific methylation marker for OSCC.

methodsWe selected OSCC datasets analyzed using the IlluminaHumanMethylation27 BeadChip from the Gene Expression Omnibus repository of the National Center for Biotechnology Information using a bioinformatics approach. From 27,578 CG dinucleotide (CpG) sites, the CpG site with the highest difference in methylation level between healthy and cancerous cells was selected for further validation. A total of 18 mucosal tissue samples were collected from nine healthy controls and nine from OSCC subjects and subjected to microdissection for cell purification, followed by DNA extraction, bisulfite conversion, and pyrosequencing. Additionally, epithelial cells were collected from 2 cohorts including oral rinse from healthy controls, oral rinse and oral swab from OSCC subjects and oral rinse from oropharyngeal squamous cell carcinoma (SCC) were examined for their methylation status using real-time polymerase chain reaction (PCR).

resultsAmong the 27,578 differentially methylated CpG sites, cg01009664 of the thyrotropin-releasing hormone (TRH) gene showed the greatest difference in methylation level between healthy and cancerous cells. Validation of the TRH gene using pyrosequencing revealed a methylation percentage of 7% ± 3.43% in healthy cells in contrast to 63% ± 19.81% in cancerous cells. Screening of epithelial cells using real-time PCR showed that the DNA methylation level was significantly higher in oral swab and rinse samples collected from OSCC and oropharyngeal SCC subjects than those from healthy controls (p < 0.001). In addition, when using a cutoff at 3.31 ng/μL, the TRH methylation biomarker was able to distinguish OSCC and oropharyngeal SCC subjects from healthy controls with high level of area under the curve, sensitivity and specificity.

conclusionWe demonstrated cg01009664 of TRH as a potential biomarker for OSCC and oropharyngeal SCC screening using oral rinse and swab techniques.

Indexed as

DNA MethylationBiomarkers, TumorCase-Control StudiesCpG IslandsDatabases, GeneticEarly Detection of CancerEpigenesis, GeneticFemaleGenetic Predisposition to DiseaseHumansMaleMouth NeoplasmsOropharyngeal NeoplasmsPredictive Value of TestsReal-Time Polymerase Chain ReactionReproducibility of ResultsBiomarkers, TumorThyrotropin-Releasing HormoneBioinformaticsDNA methylationOral cancerPyrosequencing

Identifiers

PMID30081853
PMCPMC6080527
OpenAlexW2885113681

What OpenQuestion holds

Textmetadata
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.