Evidence map›Paper›PMID 30081852›Full record

ArticleBMC cancer2018

Aberrant DNA methylation of ADAMTS16 in colorectal and other epithelial cancers.

Felix Kordowski, Julia Kolarova, Clemens Schafmayer, Stephan Buch, Torsten Goldmann, Sebastian Marwitz, Christian Kugler, Swetlana Scheufele, Volker Gassling, Christopher G Németh and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.3field-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

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  3. Review
  4. Assessment of Methylation in SelectedInternational journal of molecular sciences · 2025
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  10. Amino acid motifs for the identification of novel protein interactants.Computational and structural biotechnology journal · 2023
    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

18 authors at 6 institutions in 1 country.

Felix KordowskiDepartment of Dermatology and Allergology, University Hospital Schleswig-Holstein, University of Kiel, Rosalind-Franklin-Straße 7, 24105, Kiel, Germany.
Julia KolarovaInstitute of Human Genetics, University of Kiel, Kiel, Germany.
Clemens SchafmayerDepartment of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Stephan BuchMedical Department 1, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
Torsten GoldmannPathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Lübeck, Germany.
Sebastian MarwitzPathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Lübeck, Germany.
Christian KuglerThoracic Surgery, LungenClinic Grosshansdorf, Grosshansdorf, Germany.
Swetlana ScheufeleInstitute of Human Genetics, University of Kiel, Kiel, Germany.
Volker GasslingDepartment of Oral and Maxillofacial Surgery, University of Kiel, Kiel, Germany.
Christopher G NémethDepartment of Oral and Maxillofacial Surgery, University of Kiel, Kiel, Germany.
Mario BroschMedical Department 1, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
Jochen HampeMedical Department 1, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
Ralph LuciusAnatomical Institute, University of Kiel, Kiel, Germany.
Christian RöderInstitute for Experimental Cancer Research, University of Kiel, Kiel, Germany.
Holger KalthoffInstitute for Experimental Cancer Research, University of Kiel, Kiel, Germany.
Reiner SiebertInstitute of Human Genetics, University of Kiel, Kiel, Germany.
Ole AmmerpohlInstitute of Human Genetics, University of Kiel, Kiel, Germany.
Karina ReissDepartment of Dermatology and Allergology, University Hospital Schleswig-Holstein, University of Kiel, Rosalind-Franklin-Straße 7, 24105, Kiel, Germany. kreiss@dermatology.uni-kiel.de.ORCID http://orcid.org/0000-0001-5140-2235
Christian-Albrechts-Universität zu Kiel · DETechnische Universität Dresden · DEUniversität Ulm · DEUniversity Hospital Schleswig-Holstein · DEResearch Center Borstel - Leibniz Lung Center · DELungenClinic Grosshansdorf · DE

Funding

NIGMS NIH HHS Y01 GM001114
6 · The paper itself

Abstract

backgroundADAMs (a disintegrin and metalloproteinase) have long been associated with tumor progression. Recent findings indicate that members of the closely related ADAMTS (ADAMs with thrombospondin motifs) family are also critically involved in carcinogenesis. Gene silencing through DNA methylation at CpG loci around e.g. transcription start or enhancer sites is a major mechanism in cancer development. Here, we aimed at identifying genes of the ADAM and ADAMTS family showing altered DNA methylation in the development or colorectal cancer (CRC) and other epithelial tumors.

methodsWe investigated potential changes of DNA methylation affecting ADAM and ADAMTS genes in 117 CRC, 40 lung cancer (LC) and 15 oral squamous-cell carcinoma (SCC) samples. Tumor tissue was analyzed in comparison to adjacent non-malignant tissue of the same patients. The methylation status of 1145 CpGs in 51 ADAM and ADAMTS genes was measured with the HumanMethylation450 BeadChip Array. ADAMTS16 protein expression was analyzed in CRC samples by immunohistochemistry.

resultsIn CRC, we identified 72 CpGs in 18 genes which were significantly affected by hyper- or hypomethylation in the tumor tissue compared to the adjacent non-malignant tissue. While notable/frequent alterations in methylation patterns within ADAM genes were not observed, conspicuous changes were found in ADAMTS16 and ADAMTS2. To figure out whether these differences would be CRC specific, additional LC and SCC tissue samples were analyzed. Overall, 78 differentially methylated CpGs were found in LC and 29 in SCC. Strikingly, 8 CpGs located in the ADAMTS16 gene were commonly differentially methylated in all three cancer entities. Six CpGs in the promoter region were hypermethylated, whereas 2 CpGs in the gene body were hypomethylated indicative of gene silencing. In line with these findings, ADAMTS16 protein was strongly expressed in globlet cells and colonocytes in control tissue but not in CRC samples. Functional in vitro studies using the colorectal carcinoma cell line HT29 revealed that ADAMTS16 expression restrained tumor cell proliferation.

conclusionsWe identified ADAMTS16 as novel gene with cancer-specific promoter hypermethylation in CRC, LC and SCC patients implicating ADAMTS16 as potential biomarker for these tumors. Moreover, our results provide evidence that ADAMTS16 may have tumor suppressor properties.

Indexed as

DNA MethylationADAMTS ProteinsBiomarkers, TumorCell ProliferationColorectal NeoplasmsCpG IslandsEpigenesis, GeneticGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseHT29 CellsHumansLung NeoplasmsMouth NeoplasmsPromoter Regions, GeneticSquamous Cell Carcinoma of Head and NeckADAMTS16 protein, humanADAMTS ProteinsBiomarkers, TumorADAMTS16Colorectal cancerDNA methylationProliferation

Identifiers

PMID30081852
PMCPMC6080380
OpenAlexW2887201042

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.