Evidence map›Paper›PMID 25773145›Full record

ArticleCancer2015

Correlation of gene methylation in surgical margin imprints with locoregional recurrence in head and neck squamous cell carcinoma.

Masamichi Hayashi, Gaosong Wu, Jong-Lyel Roh, Xiaofei Chang, Xiufeng Li, Julie Ahn, Marla Goldsmith, Zubair Khan, Justin Bishop, Zhe Zhang and 4 more

Abstract read
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In one paragraph

Article in Cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
3.0field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. The impact of histology and molecular biology in refining the prognostic value of surgical margins in head and neck oncology - A narrative review.Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale · 2025
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  15. Targeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV-Positive Oropharyngeal Cancer.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2020
    Article
  16. Review
  17. Article
  18. Aberrant DNA methylation of theJournal of Cancer · 2018
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Masamichi HayashiDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Gaosong WuDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jong-Lyel RohDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Xiaofei ChangDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Xiufeng LiDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Julie AhnDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Marla GoldsmithDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Zubair KhanDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Justin BishopDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Zhe ZhangDepartment of Oncology, Biostatistics, and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Xian Chong ZhouDepartment of Oncology, Biostatistics, and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jeremy RichmonDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Nishant AgrawalDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Wayne M KochDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

TUMOR SUPPRESOR GENE PROMOTER HYPERMETHYLATION FOR DETECTION OF HEAD AND NECKP50DE019032 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI SIDRANSKY, DAVID · 2007 to 2016
$27.1M
GENETIC ALTERATIONS AS DIAGNOSTIC AND PROGNOSTIC BIOMARKR01DE013152 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI KOCH, WAYNE M · 1999 to 2013
$5.0M
NIDCR NIH HHS P50 DE019032NIDCR NIH HHS R01 DE013152NIDCR NIH HHS R01 DE013152-11
6 · The paper itself

Abstract

backgroundSecuring negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets.

methodsBisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated.

resultsTwo-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis.

conclusionsA panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery.

Indexed as

DNA MethylationBiomarkers, TumorCarcinoma, Squamous CellCohort StudiesDNA, NeoplasmGenetic Predisposition to DiseaseHead and Neck NeoplasmsHumansNeoplasm Recurrence, LocalNeoplasm, ResidualProspective StudiesSquamous Cell Carcinoma of Head and NeckBiomarkers, TumorDNA, Neoplasmhead and neck cancerlocoregional recurrencemethylationsquamous cell carcinomasurgical margin

Identifiers

PMID25773145
PMCPMC4457542
OpenAlexW1543136243

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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.