Overexpressed HDGF as an independent prognostic factor is involved in poor prognosis in Chinese patients with liver cancer 英文参考文献.docVIP

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Overexpressed HDGF as an independent prognostic factor is involved in poor prognosis in Chinese patients with liver cancer 英文参考文献.doc

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Overexpressed HDGF as an independent prognostic factor is involved in poor prognosis in Chinese patients with liver cancer 英文参考文献

Zhouetal.DiagnosticPathology2010,5:58 /content/5/1/58 RESEARCH OpenAccess OverexpressedHDGFasanindependent prognosticfactorisinvolvedinpoorprognosisin Chinesepatientswithlivercancer YanyanZhou1,NanxiangZhou1,WeiyiFang2*,JirongHuo1* Abstract Background:Hepatoma-derivedgrowthfactor(HDGF)isinvolvedinthehepatocarcinogenesis.Inthisstudy,we investigatedtheHDGFexpressioninhepatocellularcarcinoma(HCC)anditscorrelationwithclinicopathologic features,includingthesurvivalofpatientswithHCC.Furthermore,weexaminedthebiologicalprocessesregulated byHDGFduringthedevelopmentofusingHepG2celllineasamodelsystem. Methods:weusedimmunohistochemistrytocompareHDGFproteinexpressioninHCCandnormallivertissues andfurtheranalyzetheHDGFproteinexpressioninclinicopathologicallycharacterized137HCCcases.Westably knockeddowntheendogenousexpressionlevelofHDGFinHepG2cellswithspecificshRNA-expressinglentiviral vector.Followingthesuccessfulestablishmentofstablecells,weexaminedinvitrocellgrowthbyMTTassay, anchorage-independentgrowthbysoft-agarcolonyformationassayandcellmigration/invasionbytranswelland boydenchamberassay.Andinaddition,wealsoinvestigatedtheinvivotumorgrowthbyxenograft transplantationofHepG2cellsintonudemice. Results:ProteinexpressionlevelofHDGFwasmarkedlyhigherinHCCtissuesthanthatinthenormallivertissues (P=0.011).Inaddition,highexpressionofHDGFproteinwaspositivelycorrelatedwithTclassification(p0.001),N classification(p0.001),andclinicalstage(p0.001)ofHCCpatients.PatientswithhigherHDGFexpression showedasignificantlyshorteroverallsurvivaltimethandidpatientswithlowHDGFexpression.Multivariate analysissuggestedthatHDGFexpressionmightbeanindependentprognosticindicator(p0.001)forthesurvival ofpatientswithHCC.HDGF-specificshRNA(shHDGF)successfullyknockeddownitsendogenousexpressionin HepG2cells.ComparedtotheparentalandcontrolshRNA-transfected(shCtrl)HepG2cells,theshHDGFcells exhibitedsignificantlyreducedinvitrocellgrowth,anchorage-independentgrowth,cellmigrationandinvasion(p 0.05).Invivo,thexenograft