Overexpression of ZEB2 in Peritumoral Liver Tissue Correlates with Favorable Survival after Curative Resection of Hepatocellular Carcinoma 英文参考文献.docVIP

OverexpressionofZEB2inPeritumoralLiverTissue CorrelateswithFavorableSurvivalafterCurative ResectionofHepatocellularCarcinoma Mu-YanCai1,2.,Rong-ZhenLuo1,2.,Jie-WeiChen1,2.,Xiao-QingPei3,Jia-BinLu1,2,Jing-HuiHou1,2 ,Jing- PingYun1,2 * 1State Key Laboratory of Oncology in South China, Guangzhou, China, 2Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou, China, 3DepartmentofUltrasound,CancerCenter,SunYat-SenUniversity,Guangzhou,China Abstract Background: ZEB2 has been suggested to mediate EMT and disease aggressiveness in several types of human cancers. However,theexpressionpatternsofZEB2inhepatocellularcarcinoma(HCC)anditseffectonprognosisofHCCpatients treatedwithhepatectomyareunclear. Methodology/Principal Findings: In this study, the methods of tissue microarray and immunohistochemistry (IHC) were utilizedto investigateZEB2 expressionin HCCandperitumoral livertissue (PLT).Receiver operating characteristic (ROC), spearman’srankcorrelation,Kaplan-MeierplotsandCoxproportionalhazardsregressionmodelwereusedtoanalyzethe data.Up-regulatedexpressionofcytoplasmic/nuclearZEB2proteinwasobservedinthemajorityofPLTs,whencomparedto HCCs.FurtheranalysisshowedthatoverexpressionofcytoplasmicZEB2inHCCswasinverselycorrelatedwithAFPlevel, tumorsizeanddifferentiation(P,0.05).Also,overexpressionofcytoplasmicZEB2inPLTscorrelatedwithlowerAFPlevel (P,0.05).Inunivariatesurvivalanalysis,asignificantassociationbetweenoverexpressionofcytoplasmicZEB2byHCCs/PLTs andlonger patients’ survival wasfound(P,0.05).Importantly, cytoplasmic ZEB2expressionin PLTs wasevaluated asan independentprognosticfactorinmultivariateanalysis(P,0.05).Consequently,anewclinicopathologicprognosticmodel with cytoplasmic ZEB2 expression (including HCCs and PLTs) was constructed. The model could significantly stratify risk (low,intermediateandhigh)foroverallsurvival(P =0.002). Conclusions/Significance: Our findings provide a basis for the concept that cytoplasmic ZEB2 expressed by PLTs can predict