Quantitative Analysis and Diagnostic Significance of Methylated SLC19A3 DNA in the Plasma of Breast and Gastric Cancer Patients 英文参考文献.docVIP

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Quantitative Analysis and Diagnostic Significance of Methylated SLC19A3 DNA in the Plasma of Breast and Gastric Cancer Patients 英文参考文献.doc

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QuantitativeAnalysisandDiagnosticSignificanceof MethylatedSLC19A3DNAinthePlasmaofBreastand GastricCancerPatients EndersK.O.Ng1,2.,CandyP.H.Leung1.,VivianY.Shin1,ChrisL.P.Wong2,4,EdmondS.K.Ma2,4 ,Hong ChuanJin3,Kent-ManChu1,AvaKwong1,2,4,5* 1DepartmentofSurgery,TheUniversityofHongKong,HongKong,SpecialAdministrativeRegion,People’sRepublicofChina,2DepartmentofMolecularPathologyand DepartmentofSurgery,HongKongSanatoriumandHospital,HongKong,SpecialAdministrativeRegion,People’sRepublicofChina,3BiomedicalResearchCenter,Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China, 4Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong, Special AdministrativeRegion,People’sRepublicofChina,5DepartmentofSurgery,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica Abstract Background: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter andfoundthatSLC19A3 wasepigenetically down-regulatedin gastric cancer.Here, weaim todevelopanew biomarkerforcancerdiagnosisusingmethylatedSLC19A3DNAinplasma. Methodology/Principal Findings: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoterwasevaluatedbymethylation-specificqPCR.SLC19A3expressionwassignificantlydown-regulatedin80%(12/15) ofbreasttumors(P,0.005).Breasttumorshadsignificantincreaseinmethylationpercentagewhencomparedtoadjacent 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 patientsand60healthysubjects.PlasmaSLC19A3methylatedDNAlevelwaseffectiveindifferentiatingbothbreastand gastric cancer from healthy subjects. We further validated this biomarker in another independent blinded cohort of 78 plasma inc