title: Angiogenic and growth factors in gastric cancer.
abstract: BACKGROUND
  Antiangiogenic treatment is at the horizon in the palliative treatment of gastric cancer (GC), but data on proangiogenic biomarkers are still limited. The aim of this study was to analyze five proteins with a function in tumor angiogenesis: vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), follistatin, leptin, and platelet endothelial cell adhesion molecule 1 (CD31) in peripheral blood and corresponding tumor tissue.
  
  
  METHODS
  From 2008-2010, tumor tissue (n = 76) and corresponding preoperative serum (n = 69) of patients with localized GC were collected; 45 had perioperative chemotherapy. Protein serum or tumor lysate levels of these factors were measured by an angiogenesis multiplex immunoassay and correlated with response and survival.
  
  
  RESULTS
  Serum Ang-2 had prognostic relevance in the whole study population (P = 0.027). In subgroup analysis, serum VEGF and Ang-2 had prognostic relevance in primarily resected patients (P = 0.028; P = 0.048) but no association was found in neoadjuvantly treated patients. Follistatin concentration in the tumor tissue was associated with prognosis in all patients (P = 0.019). Tumor VEGF concentrations were correlated with histopathologic response (P = 0.011), with patients showing >50% remaining tumor having higher VEGF concentrations. The tissue Ang-2/VEGF ratio was significantly correlated with both clinical and histopathologic response (P = 0.029, P = 0.009). Additionally, the level of leptin in the tissue was associated with clinical response: nonresponding patients had higher leptin levels than those of responding patients (P = 0.032).
  
  
  CONCLUSIONS
  Our results show the importance of angiogenetic factors in serum and tumor tissue in GC for prognosis and treatment response. Further trials in larger patient populations are warranted for a further evaluation of proangiogenetic factors as biomarkers in gastrointestinal cancer.
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany. Electronic address: susanne.blank@med.uni-heidelberg.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Blank
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Catrin
authors.initials: C
authors.lastname: Deck
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Dreikhausen
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Giese
authors.affiliation: Institute of Transplant Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Falk
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D042501:Angiogenic Proteins / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D005260:Female; D038681:Follistatin / Q000097:blood; D005858:Germany / Q000453:epidemiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C586513:ANGPT2 protein, human; D042501:Angiogenic Proteins; D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D038681:Follistatin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenic factors; Gastric cancer; Growth factors; Prognosis; Response to chemotherapy