Allele Loss and Down-Regulation of Heparanase Gene Are Associated with the Progression and Poor Prognosis of Hepatocellular Carcinoma 英文参考文献.docVIP

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Allele Loss and Down-Regulation of Heparanase Gene Are Associated with the Progression and Poor Prognosis of Hepatocellular Carcinoma 英文参考文献.doc

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Allele Loss and Down-Regulation of Heparanase Gene Are Associated with the Progression and Poor Prognosis of Hepatocellular Carcinoma 英文参考文献

AlleleLossandDown-RegulationofHeparanaseGene AreAssociatedwiththeProgressionandPoorPrognosis ofHepatocellularCarcinoma Guo-LiangHuang1,2,Bin-KuiLi3,Mei-YinZhang1,Rong-RongWei1,Yun-FeiYuan3,MingShi3 ,Xiao- QianChen1,LongHuang1,Hui-ZhongZhang4,WanqingLiu5,Bi-JunHuang1,HonghuaLi6 ,Xiao- FengZheng6,Xian-RongLuo7,Hui-YunWang1,6* 1NationalKeyLaboratoryofOncologyinSouthChina,SunYat-SenUniversityCancerCenter,Guangzhou,Guangdong,China,2Sino-AmericanCancerResearchInstitute, GuangdongMedicalCollege,Dongguan,Guangdong,China,3DepartmentofHepatobiliaryOncology,SunYat-SenUniversityCancerCenter,Guangzhou,Guangdong, China,4DepartmentofPathology,SunYat-SenUniversityCancerCenter,Guangzhou,Guangdong,China,5SectionofHematology/Oncology,DepartmentofMedicine, UniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica,6DepartmentofPharmacology,RobertW.JohnsonMedicalSchool,UMDNJ,Piscataway,NewJersey, UnitedStatesofAmerica,7The458HospitalofPLA,Guangzhou,Guangdong,China Abstract Objectives: The role of heparanase (HPSE) gene in cancers including hepatocellular carcinoma (HCC) is currently controversial.ThisstudywasaimedatinvestigatingtheimpactofgeneticalterationandexpressionchangeofHPSEonthe progressionandprognosisofHCC. Methods:TheHPSEgenewasstudiedinthreedifferentaspects:(1)lossofheterozygosity(LOH)byacustomSNPmicroarray andDNAcopynumberbyreal-timePCR;(2)mRNAlevelbyqRT-PCR;and(3)proteinexpressionbyimmunohistochemistry. TheclinicalsignificancesofallelelossandexpressionchangeofHPSEwereanalyzed. Results:MicroarrayanalysisshowedthattheaverageLOHfrequencyfor10SNPslocatedwithinHPSEgenewas31.6%,three ofwhichweresignificantlycorrelatedwithtumorgrade,serumHBV-DNAlevel,andAFPconcentration.Inagreementwith SNPLOHdata,DNAcopynumberlossofHPSEwasobservedin38.74%(43/111)ofHCCcases.HPSEmRNAlevelwasnotably reducedin74.1%(83/112)oftumortissuescomparedwithnon-tumorlivertissues,whichwassignificantlyassociatedwith DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was