Evidence map›Paper›PMID 32285140›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2020

The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer.

Fernanda Wisnieski, Leonardo Caires Santos, Danielle Queiroz Calcagno, Jaqueline Cruz Geraldis, Carolina Oliveira Gigek, Ana Carolina Anauate, Elizabeth Suchi Chen, Lucas Trevizani Rasmussen, Spencer Luiz Marques Payão, Ricardo Artigiani and 9 more

Abstract read
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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 25 citations in OpenAlex.

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  12. Differential regulation ofEpigenetics · 2022
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  13. Peripheral Blood-basedIn vivo (Athens, Greece)
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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

19 authors at 4 institutions in 2 countries.

Fernanda WisnieskiDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil. f.wisnieski@unifesp.br.
Leonardo Caires SantosDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Danielle Queiroz CalcagnoPrograma de Pós-graduação em Oncologia e Ciências Médicas, Universidade Federal do Pará, Rua dos Mundurucus, 4487, Belém, Pará, 66073-000, Brazil.
Jaqueline Cruz GeraldisDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Carolina Oliveira GigekDepartamento de Patologia, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Ana Carolina AnauateDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Elizabeth Suchi ChenDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Lucas Trevizani RasmussenDisciplina de Genética, Hemocentro da Faculdade de Medicina de Marília, Rua Lourival Freire, 240, Marília, São Paulo, 17519-050, Brazil.
Spencer Luiz Marques PayãoDisciplina de Genética, Hemocentro da Faculdade de Medicina de Marília, Rua Lourival Freire, 240, Marília, São Paulo, 17519-050, Brazil.
Ricardo ArtigianiDepartamento de Patologia, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Samia DemachkiPrograma de Pós-graduação em Oncologia e Ciências Médicas, Universidade Federal do Pará, Rua dos Mundurucus, 4487, Belém, Pará, 66073-000, Brazil.
Paulo Pimentel AssumpçãoPrograma de Pós-graduação em Oncologia e Ciências Médicas, Universidade Federal do Pará, Rua dos Mundurucus, 4487, Belém, Pará, 66073-000, Brazil.
Laercio Gomes LourençoDisciplina de Gastroenterologia Cirúrgica, Departamento de Cirurgia, Universidade Federal de São Paulo, R. Napoleão de Barros, 715, São Paulo, 04024002, Brazil.
Carlos Haruo ArasakiDisciplina de Gastroenterologia Cirúrgica, Departamento de Cirurgia, Universidade Federal de São Paulo, R. Napoleão de Barros, 715, São Paulo, 04024002, Brazil.
Stephan PabingerAustrian Institute of Technology, Center for Health & Bioresources, Molecular Diagnostics, Giefinggasse 4, 1210, Vienna, Austria.
Julie KrainerAustrian Institute of Technology, Center for Health & Bioresources, Molecular Diagnostics, Giefinggasse 4, 1210, Vienna, Austria.
Mariana Ferreira LealDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil.
Rommel Rodriguez BurbanoPrograma de Pós-graduação em Oncologia e Ciências Médicas, Universidade Federal do Pará, Rua dos Mundurucus, 4487, Belém, Pará, 66073-000, Brazil.
Marilia Arruda Cardoso SmithDisciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo, São Paulo, 04023900, Brazil. macsmith@unifesp.br.
Universidade Federal de São Paulo · BRUniversidade Federal do Pará · BRAustrian Institute of Technology · ATFaculdade de Medicina de Marília · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Very few therapeutic options are currently available in this neoplasia. The use of 5-Aza-2'-deoxycytidine (5-AZAdC) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses. Epigenetic manipulation of GC cell lines is a useful tool to better understand gene expression regulatory mechanisms for clinical applications. Therefore, we compared the gene expression profile of 5-AZAdC-treated and untreated GC cell lines by a microarray assay. Among the genes identified in this analysis, we selected NRN1 and TNFAIP3 to be evaluated for gene expression by RT-qPCR and DNA methylation by bisulfite DNA next-generation sequencing in 43 and 52 pairs of GC and adjacent non-neoplastic tissue samples, respectively. We identified 83 candidate genes modulated by DNA methylation in GC cell lines. Increased expression of NRN1 and TNFAIP3 was associated with advanced tumours (P < 0.05). We showed that increased NRN1 and TNFAIP3 expression seems to be regulated by DNA demethylation in GC samples: inverse correlations between the mRNA and DNA methylation levels in the promoter of NRN1 (P < 0.05) and the intron of TNFAIP3 (P < 0.05) were detected. Reduced NRN1 promoter methylation was associated with III/IV TNM stage tumours (P = 0.03) and the presence of Helicobacter pylori infection (P = 0.02). The identification of demethylated activated genes in GC may be useful in clinical practice, stratifying patients who are less likely to benefit from 5-AZAdC-based therapies. KEY MESSAGES: Higher expression of NRN1 and TNFAIP3 is associated with advanced gastric cancer (GC). NRN1 promoter hypomethylation contributes to gene upregulation in advanced GC. TNFAIP3 intronic-specific CpG site demethylation contributes to gene upregulation in GC. These findings may be useful to stratify GC patients who are less likely to benefit from DNA demethylating-based therapies.

Indexed as

DNA DemethylationGene Expression Regulation, NeoplasticAzacitidineBiomarkers, TumorCell Line, TumorComputational BiologyCpG IslandsDecitabineDNA MethylationEpigenesis, GeneticGene Expression ProfilingGPI-Linked ProteinsHumansNeoplasm StagingNeuropeptidesPrognosisAzacitidineBiomarkers, TumorDecitabineGPI-Linked ProteinsNeuropeptidesNRN1 protein, humanTNFAIP3 protein, humanTumor Necrosis Factor alpha-Induced Protein 35-Aza-2′-deoxycytidineCancer therapyDNA methylationNRN1TNFAIP3

Identifiers

PMID32285140
OpenAlexW3015888876

What OpenQuestion holds

Textmetadata
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.