ASAP1ExpressioninInvasiveBreastCanceranditsPrognosticRole

Abstract

ABSTRACT ASAP1ExpressioninInvasiveBreastCancer anditsPrognosticRole

HosubPark DepartmentofMedicalScience GraduateSchoolofHanyangUniversity

Background:Breastcancerisamajorglobalhealthburdenwithhighmorbidityandmortalityrates.PreviousstudieshavereportedthatincreasedexpressionofASAP1isassociatedwithpoorprognosisinvarioustypesofcancer.Arecentstudyreportedopposingfindingsinanestrogenreceptor-positiveluminalbreastcancermousemodel.ThisstudyinvestigatedtheassociationbetweenASAP1expressionandclinicaloutcomesinbreastcancerpatients.

Methods:Thisretrospectiveanalysiswasconductedon452breastcancerpatientswhounderwentsurgeryatHanyangUniversityHospitalfrom2003to2017.Dataonclinicopathologicalcharacteristicsincludingmolecularpathologicmarkerswerecollected.ImmunohistochemicalstainingofASAP1expressionlevelwasusedtoclassifypatientsintohighandlowgroup.

Results:LowASAP1expressionwasobservedin276(61.06%)ofbreastcancercases.Inthetotal452cases,lowASAP1expressionwasassociatedwithsignificantlyworserecurrence-freesurvival(p=0.029).InER-positivecases(n=280),lowASAP1expressionwasassociatedwithsignificantlyworseoverallsurvival(p=0.039)andrecurrence-freesurvival(p=0.029).Inmultivariateanalysis,lowASAP1expressionwasanindependentsignificantpredictorofpoorrecurrence-freesurvivalintheoverallpatientgroup(hazardratio=2.566,p=0.002)andER-positivecases(hazardratio=4.046,p=0.002).IntheanalysisoftheTCGAdataset,lowexpressiongroupofASAP1proteindemonstratedsignificantlypoorerprogression-freesurvival(p=0.005).

Conclusions:LowASAP1expressionwasassociatedwithworserecurrence-freesurvivalininvasivebreastcancer.ASAP1expressionmayserveasapotentialprognosticbiomarkerforpersonalizedtreatmentdecisionsinbreastcancerpatients. |국문요지

침윤성유방암에서ASAP1단백질발현과예후와의연관성

박호섭 의학과 한양대학교대학원

연구배경:유방암은높은발병률과사망률로인해전세계적으로주요한건강문제로대두되고있다.다수의이전연구들에서ASAP1발현증가가다양한종류의암에서불량한예후와연관되어있다고보고되었다.그러나에스트로겐수용체양성유방암마우스모델을이용한최근의연구에서는반대로ASAP1의발현소실이불량한예후와연관됨을보고하였다.본연구에서는유방암환자에서ASAP1발현과임상병리학적인자와의상관관계,그리고환자의예후와의연관성을조사하였다.

방법:2003년부터2017년까지한양대학교병원에서유방절제술을받은452명의여성유방암환자들을대상으로후향적연구를수행하였다.분자병리학적표지자를포함한임상병리학적특성에대한데이터가수집되었다.대상환자들의진단에사용되고남은암병변의파라핀블록에서ASAP1에대한면역조직화학적염색을시행하여ASAP1단백질발현량을측정하여,고발현군과저발현군으로나누어다양한임상병리학적인자및예후와의연관성을검토하였다.

결과:전체452개유방암증례중276증례(61.06%)가ASAP1저발현군으로분류되었다.이중ASAP1저발현군에서유의하게불량한recurrence-freesurvival(p=0.029)이관찰되었다.ER-양성케이스(n=280)만따로분석한결과에서도,ASAP1저발현군에서유의하게불량한overallsurvival(p=0.039)과recurrence-freesurvival(p=0.029)이관찰되었다.재발에대한다변량COX분석에서ASAP1발현량이낮은것은전체환자그룹(n=452)및ER-양성증례(n=280)에서모두독립적으로유의한예측인자로나타났다.(Riskratio=2.566,p=0.002;Riskratio=4.046,p=0.002).TCGAdataset에대한분석에서도ASAP1단백질저발현군에서유의하게불량한progression-freesurvival(p=0.005)을보이는것이관찰되었다.

결론:ASAP1의저발현은침윤성유방암에서불량한recurrence-freesurvial과연관됨을관찰하였다.ASAP1단백질은유방암환자의개인화된치료결정을위한잠재적인재발예측인자로사용될수있으리라생각된다.