A long-range interactive DNA methylation marker panel for the promotersof HOXA9 and HOXA10 predicts survival in breast cancer patients

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473695.do
DOI
10.1186/s13148-017-0373-z
Title
A long-range interactive DNA methylation marker panel for the promotersof HOXA9 and HOXA10 predicts survival in breast cancer patients
Description
This work was supported by grants from the National Cancer Center(NCC-1611800, NCC-1410300, NCC-1710260).
abstract
Background: Most DNA cancer methylation markers are based on the transcriptional regulation of the promoter-gene relationship. Recently, the importance of long-range interactions between distal CpGs and target genes has been revealed. Here, we attempted to identify methylation markers for breast cancer that interact with distant genes.
Results: We performed integrated analysis using chromatin interactome data, methylome data, transcriptome data, and clinical information for breast cancer from public databases. Using the chromatin interactome and methylome data, we defined CpG-distant target gene relationships. After determining the differences in methylation between tumor and paired normal samples, the survival association, and the correlation between CpG methylation and distant target gene expression, we selected CpG methylation marker candidates. Using Cox proportional hazards models, we combined the selected markers and evaluated the prognostic model. We identified six methylation markers in HOXA9 and HOXA10 promoter regions and their long-range target genes. We experimentally validated the chromatin interactions, methylation status, and transcriptional regulation. A prognostic model showed that the combination of six methylation markers was highly associated with poor survival in independent datasets. According to our multivariate analysis, the prognostic model showed significantly better prognostic ability than other histological and molecular markers.
Conclusions: The combination of long-range interacting HOXA9 and HOXA10 promoter CpGs predicted the survival of breast cancer patients, providing a comprehensive and novel approach for discovering new methylation markers.
provenance
Made available in Cube on 2018-09-28T10:26:25Z (GMT). No. of bitstreams: 0
language
English
author
Park, Seong-Min
Choi, Eun-Young
Bae, Mingyun
Choi, Jung Kyoon
Kim, Youn-Jae
accessioned
2018-09-28T10:26:25Z
available
2018-09-28T10:26:25Z
issued
2017
citation
CLINICAL EPIGENETICS(9)
issn
1868-7083
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473695.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345273950
Jurisdiction
Rep.of Korea
Project Name
Biomedical Convergence Techonology
rights
openAccess
subject
Biomarker
Prognosis
DNA methylation
Survival
Long-range interaction
Chromatin interaction
HOXA9
HOXA10
type
article


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