title: A gene signature combining the tissue expression of three angiogenic factors is a prognostic marker in early-stage non-small cell lung cancer.
abstract: BACKGROUND
  Angiogenesis and lymphangiogenesis are key mechanisms for tumor growth and dissemination. They are mainly regulated by the vascular endothelial growth factor (VEGF) family of ligands and receptors. The aim of this study was to analyze relative expression levels of angiogenic markers in resectable non-small cell lung cancer patients in order to asses a prognostic signature that could improve characterization of patients with worse clinical outcomes.
  
  
  METHODS
  RNA was obtained from tumor and normal lung specimens from 175 patients. Quantitative polymerase chain reaction was performed to analyze the relative expression of HIF1A, PlGF, VEGFA, VEGFA165b, VEGFB, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, NRP1 and NRP2.
  
  
  RESULTS
  Univariate analysis showed that tumor size and ECOG-PS are prognostic factors for time to progression (TTP) and overall survival (OS). This analysis in the case of angiogenic factors also revealed that PlGF, VEGFA, VEGFB and VEGFD distinguish patients with different outcomes. Taking into account the complex interplay between the different ligands of the VEGF family and to more precisely predict the outcome of the patients, we considered a new analysis combining several VEGF ligands. In order to find independent prognostic variables, we performed a multivariate Cox analysis, which showed that the subgroup of patients with higher relative expression of VEGFA plus lower VEGFB and VEGFD presented the poorest outcome for both TTP and OS.
  
  
  CONCLUSIONS
  The relative expression of these three genes can be considered as an angiogenic gene signature whose applicability for the selection of candidates for targeted therapies needs to be further validated.
authors.affiliation: Molecular Oncology Laboratory, Fundación Investigación, Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Sanmartín
authors.forename: Rafael
authors.initials: R
authors.lastname: Sirera
authors.forename: Marta
authors.initials: M
authors.lastname: Usó
authors.forename: Ana
authors.initials: A
authors.lastname: Blasco
authors.forename: Sandra
authors.initials: S
authors.lastname: Gallach
authors.forename: Santiago
authors.initials: S
authors.lastname: Figueroa
authors.forename: Nieves
authors.initials: N
authors.lastname: Martínez
authors.forename: Cristina
authors.initials: C
authors.lastname: Hernando
authors.forename: Antonio
authors.initials: A
authors.lastname: Honguero
authors.forename: Miguel
authors.initials: M
authors.lastname: Martorell
authors.forename: Ricardo
authors.initials: R
authors.lastname: Guijarro
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Eloisa
authors.initials: E
authors.lastname: Jantus-Lewintre
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C467484:VEGFA protein, human; C467485:VEGFB protein, human; C579459:VEGFD protein, human; D042461:Vascular Endothelial Growth Factor A; D042561:Vascular Endothelial Growth Factor B; D042643:Vascular Endothelial Growth Factor D