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Article: Quantitative analysis and diagnostic significance of methylated SLC19A3 DNA in the plasma of breast and gastric cancer patients

TitleQuantitative analysis and diagnostic significance of methylated SLC19A3 DNA in the plasma of breast and gastric cancer patients
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 7 How to Cite?
AbstractBackground: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma. Methodology/Principal Findings: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. SLC19A3 expression was significantly down-regulated in 80% (12/15) of breast tumors (P<0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P<0.005). A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR (MSRED-qPCR) was developed to quantify SLC19A3 DNA methylation in plasma. We validated this biomarker in an independent validation cohort of 165 case-control plasma including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects. Plasma SLC19A3 methylated DNA level was effective in differentiating both breast and gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma including 38 breast cancer, 20 gastric cancer patients and 20 healthy subjects. The positive predictive values for breast and gastric cancer were 90% and 85%, respectively. The negative predictive value of this biomarker was 85%. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 100%. Conclusions: These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis. © 2011 Ng et al.
Persistent Identifierhttp://hdl.handle.net/10722/144561
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong10400959
Dr. Ellen Li Charitable Foundation
Funding Information:

The University of Hong Kong Seed Fund for Basic Research 2009 (Ref #: 10400959). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorLeung, CPHen_HK
dc.contributor.authorShin, VYen_HK
dc.contributor.authorWong, CLPen_HK
dc.contributor.authorMa, ESKen_HK
dc.contributor.authorJin, HCen_HK
dc.contributor.authorChu, KMen_HK
dc.contributor.authorKwong, Aen_HK
dc.date.accessioned2012-02-03T06:13:52Z-
dc.date.available2012-02-03T06:13:52Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 7en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144561-
dc.description.abstractBackground: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma. Methodology/Principal Findings: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. SLC19A3 expression was significantly down-regulated in 80% (12/15) of breast tumors (P<0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P<0.005). A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR (MSRED-qPCR) was developed to quantify SLC19A3 DNA methylation in plasma. We validated this biomarker in an independent validation cohort of 165 case-control plasma including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects. Plasma SLC19A3 methylated DNA level was effective in differentiating both breast and gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma including 38 breast cancer, 20 gastric cancer patients and 20 healthy subjects. The positive predictive values for breast and gastric cancer were 90% and 85%, respectively. The negative predictive value of this biomarker was 85%. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 100%. Conclusions: These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for breast and gastric cancer diagnosis. © 2011 Ng et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshBreast Neoplasms - blood - diagnosis - genetics - pathology-
dc.subject.meshDNA Methylation - genetics-
dc.subject.meshDown-Regulation - genetics-
dc.subject.meshMembrane Transport Proteins - genetics-
dc.subject.meshStomach Neoplasms - blood - diagnosis - genetics - pathology-
dc.titleQuantitative analysis and diagnostic significance of methylated SLC19A3 DNA in the plasma of breast and gastric cancer patientsen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.emailKwong, A: avakwong@hkucc.hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.identifier.authorityKwong, A=rp01734en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0022233en_HK
dc.identifier.pmid21789241-
dc.identifier.pmcidPMC3138782-
dc.identifier.scopuseid_2-s2.0-79960611738en_HK
dc.identifier.hkuros198394en_US
dc.identifier.hkuros191692-
dc.identifier.hkuros191079-
dc.identifier.hkuros194561-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960611738&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue7en_HK
dc.identifier.spagee22233en_US
dc.identifier.epagee22233en_US
dc.identifier.eissn1932-6203-
dc.identifier.isiWOS:000292812400041-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridLeung, CPH=41761959600en_HK
dc.identifier.scopusauthoridShin, VY=7003491170en_HK
dc.identifier.scopusauthoridWong, CLP=8987839600en_HK
dc.identifier.scopusauthoridMa, ESK=55356328300en_HK
dc.identifier.scopusauthoridJin, HC=24577511700en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK
dc.identifier.scopusauthoridKwong, A=8913654300en_HK

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