Poor Prognosis of Gastric Adenocarcinoma with Decreased Expression of AHRR 英文参考文献.docVIP

PoorPrognosisofGastricAdenocarcinomawith DecreasedExpressionofAHRR Yuan-fangLi1,2.,Dan-danWang1.,Bai-weiZhao1,2.,WeiWang1,2,Shu-qiangYuan1,2,Chun-yuHuang1,2 , Yong-mingChen1,2,YanZheng1,2,RajivPrasadKeshari1,2,Jian-chuanXia1*,Zhi-weiZhou1,2* 1StateKeyLaboratoryofOncologyinSouthChinaandDepartmentofExperimentalResearch,SunYat-senUniversityCancerCenter,Guangzhou,People’sRepublicof China,2DepartmentofGastricandPancreaticSurgery,SunYat-senUniversityCancerCenter,Guangzhou,People’sRepublicofChina Abstract Background: The aryl hydrocarbon receptor (AHR) repressor (AHRR), a member of growing superfamily, is a basic-helix- loop-helix/Per-AHRnucleartranslocator(ARNT)-Sim(bHLH-PAS)protein.Recently,AHRRhasbeenproposedtofunctionasa putativenewtumorsuppressorgenebasedonsomerelevantstudiesinmultipletypesofhumancancers.Thiscurrentstudy aimstoinvestigateAHHRexpressionanditsprognosticsignificanceinprimarygastricadenocarcinoma. Methodology/PrincipalFindings:TheexpressionlevelofAHRRwasanalyzedusingreal-timequantitativePCR(RT-qPCR), westernblotting,andimmunohistochemicalstaining.ItwasclearlyshowedthattheexpressionstatusofAHRRwasreduced intumortissuesamplescomparedwiththatinmatchedadjacentnon-tumortissuesamplesbyRT-qPCR(P=0.0423)and western blotting analysis (P=0.004). Moreover, data revealed that AHRR without exon 8 (the active isoform) was the predominantformeitherintumortissues(66.7%,8/12)orinmatchedadjacentnon-tumortissues(100.0%,12/12),andthe mRNAlevelofthisisoformwassignificantlyreducedintumortissues(P=0.006).Immunohistochemistryanalysisindicated thatAHRRexpressionwassignificantlydecreasedin175of410(42.7%)gastricadenocarcinomacases.Kaplan-Meiersurvival curves and Multivariate Cox analysis revealed that decreased expression of AHRR was significantly associated with poor prognosisingastricadenocarcinomapatients. Conclusions/Significance:Ourdatasuggeststhat,inprimarygastricadenocarcinoma,AHRRmayplayasasuppressorgene anditsexpressionstatushasthepotentialtobeanindependentprognosticfact