Evidence map›Paper›PMID 30987631›Full record

ArticleBMC medical genomics2019

Genes CEP55, FOXD3, FOXF2, GNAO1, GRIA4, and KCNA5 as potential diagnostic biomarkers in colorectal cancer.

Nina Hauptman, Daša Jevšinek Skok, Elena Spasovska, Emanuela Boštjančič, Damjan Glavač

Open access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
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  8. Association ofInternational journal of molecular sciences · 2023
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  10. HypermethylatedFrontiers in oncology · 2023
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  16. Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer.Evidence-based complementary and alternative medicine : eCAM · 2022
    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

5 authors at 1 institution in 1 country.

Nina HauptmanInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000, Ljubljana, Slovenia. nina.hauptman@mf.uni-lj.si.ORCID 0000-0002-7575-7716
Daša Jevšinek SkokInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000, Ljubljana, Slovenia.
Elena SpasovskaInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000, Ljubljana, Slovenia.
Emanuela BoštjančičInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000, Ljubljana, Slovenia.
Damjan GlavačInstitute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, SI-1000, Ljubljana, Slovenia.
University of Ljubljana · SI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) is one of the leading causes of death by cancer worldwide and in need of novel potential diagnostic biomarkers for early discovery.

methodsWe conducted a two-step study. We first employed bioinformatics on data from The Cancer Genome Atlas to obtain potential biomarkers and then experimentally validated some of them on our clinical samples. Our aim was to find a methylation alteration common to all clusters, with the potential of becoming a diagnostic biomarker in CRC.

resultsUnsupervised clustering of methylation data resulted in four clusters, none of which had a known common genetic or epigenetic event, such as mutations or methylation. The intersect among clusters and regulatory regions resulted in 590 aberrantly methylated probes, belonging to 198 differentially expressed genes. After performing pathway and functional analysis on differentially expressed genes, we selected six genes: CEP55, FOXD3, FOXF2, GNAO1, GRIA4 and KCNA5, for further experimental validation on our own clinical samples. In silico analysis demonstrated that CEP55 was hypomethylated in 98.7% and up-regulated in 95.0% of samples. Genes FOXD3, FOXF2, GNAO1, GRIA4 and KCNA5 were hypermethylated in 97.9, 81.1, 80.3, 98.4 and 94.0%, and down-regulated in 98.3, 98.9, 98.1, 98.1 and 98.6% of samples, respectively. Our experimental data show CEP55 was hypomethylated in 97.3% of samples and down-regulated in all samples, while FOXD3, FOXF2, GNAO1, GRIA4 and KCNA5 were hypermethylated in 100.0, 90.2, 100.0, 99.1 and 100.0%, and down-regulated in 68.0, 76.0, 96.0, 95.2 and 84.0% of samples, respectively. Results of in silico and our experimental analyses showed that more than 97% of samples had at least four methylation markers altered.

conclusionsUsing bioinformatics followed by experimental validation, we identified a set of six genes that were differentially expressed in CRC compared to normal mucosa and whose expression seems to be methylation dependent. Moreover, all of these six genes were common in all methylation clusters and mutation statuses of CRC and as such are believed to be an early event in human CRC carcinogenesis and to represent potential CRC biomarkers.

Indexed as

AdultBiomarkers, TumorCell Cycle ProteinsColorectal NeoplasmsComputational BiologyDNA MethylationFemaleForkhead Transcription FactorsGene Expression Regulation, NeoplasticGTP-Binding Protein alpha Subunits, Gi-GoHumansKv1.5 Potassium ChannelMaleReceptors, AMPABiomarkers, TumorCell Cycle ProteinsCep55 protein, humanForkhead Transcription FactorsFOXD3 protein, humanFOXF2 protein, humanglutamate receptor ionotropic, AMPA 4GNAO1 protein, humanGTP-Binding Protein alpha Subunits, Gi-GoKv1.5 Potassium ChannelReceptors, AMPABioinformatics approachColorectal cancerExperimental validationExpressionMethylation

Identifiers

PMID30987631
PMCPMC6466812
OpenAlexW2946180777

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.