Evidence map›Paper›PMID 27738327›Full record

ArticleOncotarget2016

Genome-wide methylome analysis using MethylCap-seq uncovers 4 hypermethylated markers with high sensitivity for both adeno- and squamous-cell cervical carcinoma.

Rong Wang, Robert W van Leeuwen, Aniek Boers, Harry G Klip, Tim de Meyer, Renske D M Steenbergen, Wim van Criekinge, Ate G J van der Zee, Ed Schuuring, G Bea A Wisman

Abstract readValidation Study
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. PAX1 and ZNF582 Methylation as a Triage Strategy in Cytologic and hrHPV+ Scrapings in Both Chinese and Dutch Cohorts.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
  3. Article
  4. Identification of a novel hypermethylation marker, ZSCAN18, and construction of a diagnostic model in cervical cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
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  9. Frontiers in genetics · 2020
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  10. Cancer biology & medicine · 2019
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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

10 authors.

Rong WangDepartment of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.
Robert W van LeeuwenDepartment of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.
Aniek BoersDepartment of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.
Harry G KlipDepartment of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.
Tim de MeyerDepartment of Mathematical Modeling, Statistics and Bio-informatics, University of Ghent, Ghent, Belgium.
Renske D M SteenbergenDepartment of Pathology, VU University Medical Centre, Amsterdam, The Netherlands.
Wim van CriekingeDepartment of Mathematical Modeling, Statistics and Bio-informatics, University of Ghent, Ghent, Belgium.
Ate G J van der ZeeDepartment of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.
Ed SchuuringDepartment of Pathology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.
G Bea A WismanDepartment of Gynecologic Oncology, University of Groningen, University Medical Centre Groningen, Cancer Research Centre Groningen, Groningen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCytology-based screening methods for cervical adenocarcinoma (ADC) and to a lesser extent squamous-cell carcinoma (SCC) suffer from low sensitivity. DNA hypermethylation analysis in cervical scrapings may improve detection of SCC, but few methylation markers have been described for ADC. We aimed to identify novel methylation markers for the early detection of both ADC and SCC.

resultsGenome-wide methylation profiling for 20 normal cervices, 6 ADC and 6 SCC using MethylCap-seq yielded 53 candidate regions hypermethylated in both ADC and SCC. Verification and independent validation of the 15 most significant regions revealed 5 markers with differential methylation between 17 normals and 13 cancers. Quantitative methylation-specific PCR on cervical cancer scrapings resulted in detection rates ranging between 80% and 92% while between 94% and 99% of control scrapings tested negative. Four markers (SLC6A5, SOX1, SOX14 and TBX20) detected ADC and SCC with similar sensitivity. In scrapings from women referred with an abnormal smear (n=229), CIN3+ sensitivity was between 36% and 71%, while between 71% and 93% of adenocarcinoma in situ (AdCIS) were detected; and CIN0/1 specificity was between 88% and 98%. Compared to hrHPV, the combination SOX1/SOX14 showed a similar CIN3+ sensitivity (80% vs. 75%, respectively, P>0.2), while specificity improved (42% vs. 84%, respectively, P < 10-5).

conclusionSOX1 and SOX14 are methylation biomarkers applicable for screening of all cervical cancer types.

Indexed as

DNA MethylationAdenocarcinoma in SituAdultAgedBiomarkers, TumorCarcinoma, AdenosquamousCarcinoma, Squamous CellCase-Control StudiesEarly Detection of CancerFemaleGene Expression ProfilingGenetic Predisposition to DiseaseGenome-Wide Association StudyGlial Cell Line-Derived Neurotrophic Factor ReceptorsGlycine Plasma Membrane Transport ProteinsHumansBiomarkers, TumorGFRA1 protein, humanGlial Cell Line-Derived Neurotrophic Factor ReceptorsGlycine Plasma Membrane Transport ProteinsSLC6A5 protein, humanSOX14 protein, humanSOX1 protein, humanSOXB1 Transcription FactorsSOXB2 Transcription FactorsT-Box Domain ProteinsTBX20 protein, humanadenocarcinoma (in situ)DNA methylation biomarkersMethylCap-seq(quantitative) methylation-specific PCR ((Q)MSP)uterine cervical neoplasms

Identifiers

PMID27738327
PMCPMC5348351

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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.