Clinical and biological significance of a − 73A > C variation in the CDH1 promoter of patients with sporadic gastric ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07

AUTHORS

Baozhen Zhang, Jing Zhou, Zhaojun Liu, Liankun Gu, Jiafu Ji, Woo Ho Kim, Dajun Deng

ABSTRACT

BACKGROUND: CDH1 germline mutations lead to hereditary diffuse gastric carcinomas. However, it is unclear whether genetic variations in the CDH1 promoter affect the progression of sporadic gastric carcinomas (SGCs). METHODS: SGC patients in two independent cohorts with follow-up data were enrolled. The CDH1 genotypes, including the - 73A > C polymorphism (rs28372783), were determined by PCR sequencing. The CDH1 promoter activity was determined using reporter assays. SNAIL bound to CDH1 alleles was determined by chromatin immunoprecipitation primer extension PCR. CDH1 DNA methylation was determined by bisulfite-based PCR analyses. RESULTS: Kaplan-Meier analyses showed that the overall survival (OS) of the - 73C/C patients was significantly longer than that of the - 73A/C or - 73A/A patients in a Chinese cohort [n = 526; hazard ratio 0.68 (95% CI 0.47-1.00)], which was validated in an independent Korea cohort [n = 215; hazard ratio 0.49 (95% CI 0.26-0.94)]. Moreover, the transcription activity of the - 73C alleles was significantly higher than that of the - 73A alleles in vitro and in vivo. The ratio of SNAIL recruited to the promoter regions of the - 73C and - 73A alleles was 1:10, indicating a strong influence of this polymorphism on the recruitment of SNAIL to the flanking E-box. The prevalence of DNA methylation of the CpG island and shore within the promoter of the - 73C allele was much less than that of the - 73A allele in both gastric tissues and cancer cell lines. CONCLUSION: The - 73A > C variation may lead to differences in the overall survival of SGC patients and allele-specific repressions of CDH1. More... »

PAGES

606-616

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10120-017-0778-6

DOI

http://dx.doi.org/10.1007/s10120-017-0778-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092905120

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29168119


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10120-017-0778-6'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10120-017-0778-6'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10120-017-0778-6'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10120-017-0778-6'


 

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