Evidence map›Paper›PMID 31775891›Full record

ArticleClinical epigenetics2019

Ovarian cancer detection by DNA methylation in cervical scrapings.

Tzu-I Wu, Rui-Lan Huang, Po-Hsuan Su, Shih-Peng Mao, Chen-Hsuan Wu, Hung-Cheng Lai

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Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
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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

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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

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

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4 · The record

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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

6 authors.

Tzu-I WuDepartment of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Rui-Lan HuangDepartment of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Po-Hsuan SuTranslational Epigenetic Center, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.
Shih-Peng MaoDepartment of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, New Taipei, Taiwan.
Chen-Hsuan WuGraduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Hung-Cheng LaiDepartment of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. hclai30656@gmail.com.ORCID 0000-0001-8048-3943

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOvarian cancer (OC) is the most lethal gynecological cancer, worldwide, largely due to its vague and nonspecific early stage symptoms, resulting in most tumors being found at advanced stages. Moreover, due to its relative rarity, there are currently no satisfactory methods for OC screening, which remains a controversial and cost-prohibitive issue. Here, we demonstrate that Papanicolaou test (Pap test) cervical scrapings, instead of blood, can reveal genetic/epigenetic information for OC detection, using specific and sensitive DNA methylation biomarkers.

resultsWe analyzed the methylomes of tissues (50 OC tissues versus 6 normal ovarian epithelia) and cervical scrapings (5 OC patients versus 10 normal controls), and integrated public methylomic datasets, including 79 OC tissues and 6 normal tubal epithelia. Differentially methylated genes were further classified by unsupervised hierarchical clustering, and each candidate biomarker gene was verified in both OC tissues and cervical scrapings by either quantitative methylation-specific polymerase chain reaction (qMSP) or bisulfite pyrosequencing. A risk-score by logistic regression was generated for clinical application. One hundred fifty-one genes were classified into four clusters, and nine candidate hypermethylated genes from these four clusters were selected. Among these, four genes fulfilled our selection criteria and were validated in training and testing set, respectively. The OC detection accuracy was demonstrated by area under the receiver operating characteristic curves (AUCs) in 0.80-0.83 of AMPD3, 0.79-0.85 of AOX1, 0.78-0.88 of NRN1, and 0.82-0.85 of TBX15. From this, we found OC-risk score, equation generated by logistic regression in training set and validated an OC-associated panel comprising AMPD3, NRN1, and TBX15, reaching a sensitivity of 81%, specificity of 84%, and OC detection accuracy of 0.91 (95% CI, 0.82-1) in testing set.

conclusionsOvarian cancer detection from cervical scrapings is feasible, using particularly promising epigenetic biomarkers such as AMPD3/NRN1/TBX15. Further validation is warranted.

Indexed as

DNA MethylationAdultAgedAged, 80 and overAMP DeaminaseBiomarkers, TumorCase-Control StudiesCluster AnalysisCpG IslandsEarly Detection of CancerFemaleGPI-Linked ProteinsHumansMiddle AgedNeuropeptidesOvarian NeoplasmsAMP DeaminaseBiomarkers, TumorGPI-Linked ProteinsNeuropeptidesNRN1 protein, humanT-Box Domain ProteinsTBX15 protein, humanCancer detectionCervical scrapingsDNA methylationOvarian cancer

Identifiers

PMID31775891
PMCPMC6881994

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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.