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Coupled genome-wide DNA methylation and transcription analysis identified rich biomarkers and drug targets in triple-negative breast cancer
Guo,Maoni; Sinha,Siddharth; Wang,San Ming
2019-11-01
Source PublicationCancers
Volume11Issue:11
AbstractTriple-negative breast cancer (TNBC) has poor clinical prognosis. Lack of TNBC-specific biomarkers prevents active clinical intervention. We reasoned that TNBC must have its specific signature due to the lack of three key receptors to distinguish TNBC from other types of breast cancer. We also reasoned that coupling methylation and gene expression as a single unit may increase the specificity for the detected TNBC signatures. We further reasoned that choosing the proper controls may be critical to increasing the sensitivity to identify TNBC-specific signatures. Furthermore, we also considered that specific drugs could target the detected TNBC-specific signatures. We developed a system to identify potential TNBC signatures. It consisted of (1) coupling methylation and expression changes in TNBC to identify the methylation-regulated signature genes for TNBC; (2) using TPBC (triple-positive breast cancer) as the control to detect TNBC-specific signature genes; (3) searching in the drug database to identify those targeting TNBC signature genes. Using this system, we identified 114 genes with both altered methylation and expression, and 356 existing drugs targeting 10 of the 114 genes. Through docking and molecular dynamics simulation, we determined the structural basis between sapropterin, a drug used in the treatment of tetrahydrobiopterin deficiency, and PTGS2, a TNBC signature gene involved in the conversion of arachidonic acid to prostaglandins. Our study reveals the existence of rich TNBC-specific signatures, and many can be drug target and biomarker candidates for clinical applications.
KeywordDNA methylation Gene expression Therapeutic targets TNBC
DOI10.3390/cancers11111724
URLView the original
Language英语
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorWang,San Ming
AffiliationCancer Centre and Institute of Translational Medicine,Faculty of Health Sciences,University of Macau,Macau,999078,China
First Author AffilicationCancer Centre
Corresponding Author AffilicationCancer Centre
Recommended Citation
GB/T 7714
Guo,Maoni,Sinha,Siddharth,Wang,San Ming. Coupled genome-wide DNA methylation and transcription analysis identified rich biomarkers and drug targets in triple-negative breast cancer[J]. Cancers,2019,11(11).
APA Guo,Maoni,Sinha,Siddharth,&Wang,San Ming.(2019).Coupled genome-wide DNA methylation and transcription analysis identified rich biomarkers and drug targets in triple-negative breast cancer.Cancers,11(11).
MLA Guo,Maoni,et al."Coupled genome-wide DNA methylation and transcription analysis identified rich biomarkers and drug targets in triple-negative breast cancer".Cancers 11.11(2019).
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