Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma VEGF-A Impact Is Strongly Associated with Ang-2 英文参考文献.docVIP

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Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma VEGF-A Impact Is Strongly Associated with Ang-2 英文参考文献.doc

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Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma VEGF-A Impact Is Strongly Associated with Ang-2 英文参考文献

PrognosticImpactsofAngiopoietinsinNSCLCTumor CellsandStroma:VEGF-AImpactIsStronglyAssociated withAng-2 SigveAndersen1,2*,TomDonnem1,2,KhalidAl-Shibli3,4,SamerAl-Saad3,5,HelgeStenvold1,2 , Lill-ToveBusund3,5,RoyM.Bremnes1,2 1InstituteofClinicalMedicine,UniversityofTromso,Tromso,Norway,2DepartmentofOncology,UniversityHospitalofNorthNorway,Tromso,Norway,3Instituteof MedicalBiology,University ofTromso,Tromso,Norway,4DepartmentofPathology, NordlandCentralHospital, Bodo,Norway,5Department ofPathology,University HospitalofNorthNorway,Tromso,Norway Abstract Introduction:AngiopoietinsandtheirreceptorTie-2are,inconcertwithVEGF-A,keymediatorsinangiogenesis.Thisstudy evaluatestheprognosticimpactofallknownhumanangiopoietins(Ang-1,Ang-2andAng-4)andtheirreceptorTie-2,as wellastheirrelationtotheprognosticexpressionofVEGF-A. Methods:335unselectedstageI-IIIANSCLC-patientswereincludedandtissuesamplesofrespectivetumorcellsandstroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expressionofmarkersinduplicatetumorandstromacores. Principal Findings:Inunivariateanalyses,lowtumorcellexpressionofAng-4 (P=0.046)andlowstromalexpressions of Ang-4(P=0.009)andAng-2(P=0.017)wereindividuallyassociatedwithapoorsurvival.Inthemultivariateanalysis,low stromalAng-2(HR1.88;CI95%1.15-3.08)andAng-4(HR1.47,CI95%1.02–2.11,P=0.04)expressionswereindependently associatedwithapoorprognosis.InpatientswithhightumorcellexpressionofAng-2,aconcomitantlyhightumorVEGF-A expression mediated a dramatic survival reduction (P,0.001). In the multivariate analysis of patients with high Ang-2 expression, high tumor VEGF-A expression appeared an independent poor prognosticator (HR 6.43; CI 95% 2.46–16.8; P,0.001). Conclusions:Intumorcells,onlyAng-4expressionhasprognosticimpactinNSCLC.Intumorstroma,Ang-4andAng-2are independentlyassociatedwithsurvival.TheprognosticimpactoftumorcellVEGF-AinNSCLCappearsstronglyassociated withaconcomitantlyhightumo