Evidence map›Paper›PMID 26490796›Full record

ArticleOral oncology2015

Epigenetic screening of salivary gland mucoepidermoid carcinoma identifies hypomethylation of CLIC3 as a common alteration.

Zhiming Wang, Shizhang Ling, Eleni Rettig, Ryan Sobel, Marietta Tan, Elana J Fertig, Michael Considine, Adel K El-Naggar, Mariana Brait, Carole Fakhry and 1 more

Abstract read
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In one paragraph

Article in Oral oncology, 2015. 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
1.2field-weighted citation impact, top 20% 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, 22 citations in OpenAlex.

  1. Epigenetic alterations in head and neck cancer: a brief update.Virchows Archiv : an international journal of pathology · 2026
    Review
  2. Article
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  5. Chloride intracellular channels in oncology as potential novel biomarkers and personalized therapy targets: a systematic review.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2024
    Review
  6. Review
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  8. Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.Reviews of physiology, biochemistry and pharmacology · 2021
    Review
  9. Article
  10. Review
  11. Article
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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

11 authors at 3 institutions in 2 countries.

Zhiming WangDepartment of Oral and Maxillofacial Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA. Electronic address: wangzm@sj-hospital.org.
Shizhang LingDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA.
Eleni RettigDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA.
Ryan SobelDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA.
Marietta TanDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA.
Elana J FertigDepartment of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD, USA.
Michael ConsidineDepartment of Oncology Biostatistics, Johns Hopkins University, Baltimore, MD, USA.
Adel K El-NaggarDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mariana BraitDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA.
Carole FakhryDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA; Milton J. Dance Jr. Head and Neck Center at the Greater Baltimore Medical Center, Baltimore, MD, USA.
Patrick K HaDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, USA; Milton J. Dance Jr. Head and Neck Center at the Greater Baltimore Medical Center, Baltimore, MD, USA. Electronic address: pha1@jhmi.edu.
Johns Hopkins University · USGreater Baltimore Medical Center · USThe University of Texas MD Anderson Cancer Center · US

Funding

Molecular and Epidemiologic Characterization of Salivary Gland CarcinomasU01DE019765 · NIDCR · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI EL-NAGGAR, ADEL K. · 2009 to 2013
$6.9M
NIDCR NIH HHS U01 DE019765NIH HHS U01-RDCRC,OD-08-001
6 · The paper itself

Abstract

objectivesThe role of promoter methylation in the development of mucoepidermoid carcinoma (MEC) has not been fully explored. In this study, we investigated the epigenetic landscape of MEC.

methodsThe Illumina HumanMethylation27 BeadChip array and differential methylation analysis were utilized to screen for epigenetic alterations in 14 primary MEC tumors and 14 matched normal samples. Bisulfite sequencing was used to validate these results, with subsequent quantitative Methylation-Specific PCR (qMSP) to validate chloride intracellular channel protein 3 (CLIC3) in a separate cohort. Furthermore, CLIC3 immunohistochemical (IHC) staining was performed in another separate cohort of MEC. Finally, clinical and pathological characteristics were statistically analyzed for correlation with methylation status of CLIC3 and CLIC3 IHC H-scores by Wilcoxon rank sum, Kruskall-Wallis, and X(2) test tests.

resultsWe obtained 6 significantly differentially methylated gene candidates demonstrating significant promoter hyper- or hypo-methylation from the array data. Using bisulfite sequencing, we found one gene, CLIC3, which showed differential methylation between MEC tumor and normal samples in a small validation cohort. qMSP analysis of the CLIC3 promoter in a separate validation set showed significantly lower methylation level in tumor than in normal. The level of CLIC3 methylation in MECs was not statistically correlated with clinical or pathological characteristics. However, IHC staining intensity and distribution of CLIC3 were significantly increased in MECs, compared with those of normal salivary gland tissues.

conclusionsHypomethylation of CLIC3 promoter and its overexpression are significant events in MEC. Its functional role and potential therapeutic utility in MEC are worthy of further exploration.

Indexed as

AdultAgedCarcinoma, MucoepidermoidCase-Control StudiesChloride ChannelsDNA MethylationEpigenomicsFemaleHumansMaleMiddle AgedSalivary Gland NeoplasmsStatistics, NonparametricChloride ChannelsCLIC3 protein, humanArrayBisulfite sequencingCLIC3DNA methylationHead and neck cancerH-scoreImmunohistochemistryMethylation-specific PCRMucoepidermoid carcinoma

Identifiers

PMID26490796
PMCPMC4663116
OpenAlexW2177289342

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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.