Gene Signatures Derived from a c-MET-Driven Liver Cancer Mouse Model Predict Survival of Patients with Hepatocellular Carcinoma 英文参考文献.docVIP
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Gene Signatures Derived from a c-MET-Driven Liver Cancer Mouse Model Predict Survival of Patients with Hepatocellular Carcinoma 英文参考文献
GeneSignaturesDerivedfromac-MET-DrivenLiver
CancerMouseModelPredictSurvivalofPatientswith
HepatocellularCarcinoma
IrenaIvanovska1,4*,ChunshengZhang1,4,AngelaM.Liu2,3,KwongF.Wong3,NikkiP.Lee2 ,Patrick
Lewis1,UlrikePhilippar4,DimpleBansal4,CarolynBuser5,MartinScott4,MaoMao1¤a,RonnieT.P.Poon2,
SheungTatFan2,MicheleA.Cleary1¤b,JohnM.Luk2,3*,HongyueDai1,4
*
1RosettaInpharmaticsLLC,MerckCo.,Inc.,Seattle,Washington,UnitedStatesofAmerica,2DepartmentofSurgery,TheUniversityofHongKong,Pokfulam,Hong
Kong, China, 3Department of Pharmacology, Department of Surgery, and Cancer Science Institute, National University of Singapore, Singapore, Singapore, 4Merck
Research Laboratories, Merck Co., Inc., Boston, Massachusetts, United States of America, 5Molecular Profiling and Pharmacology, Merck Co., Inc., North Wales,
Pennsylvania,UnitedStatesofAmerica
Abstract
Biomarkers derived from gene expression profiling data may have a high false-positive rate and must be rigorously
validated using independent clinical data sets, which are not always available. Although animal model systems could
providealternativedatasetstoformulatehypothesesandlimitthenumberofsignaturestobetestedinclinicalsamples,
thepredictivepowerofsuchanapproachisnotyetproven.Thepresentstudyaimstoanalyzethemolecularsignaturesof
liver cancer in a c-MET-transgenic mouse model and investigate its prognostic relevance to human hepatocellular
carcinoma(HCC).Tissuesampleswereobtainedfromtumor(TU),adjacentnon-tumor(AN)anddistantnormal(DN)liverin
Tet-operatorregulated(TRE)humanc-METtransgenicmice(n=21)aswellasfromaChinesecohortof272HBV-and9HCV-
associated HCC patients. Whole genome microarray expression profiling was conducted in Affymetrix gene expression
chips,andprognosticsignificancesofgeneexpressionsignatureswereevaluatedacrossthetwospecies.Ourdatarevealed
parallelsbetweenmouseandhumanlivertumors,includingdown-regulationofmetabolicpathwaysandup-regulationof
cellcycleprocesses.Themousetumorsweremostsimilartoasubsetofpatients
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