title: Expression and prognostic value of circulating angiogenic cytokines in pancreatic cancer.
abstract: BACKGROUND
  The utility of circulating angiogenic cytokines (CAC) as biomarkers in pancreatic cancer has not been clarified yet. We investigated the expression and prognostic associations of seven CAC in patients with pancreatic cancer.
  
  
  METHODS
  Serum samples were collected preoperatively in patients undergoing surgery for localized pancreatic cancer (n = 74), metastatic pancreatic cancer (n = 24) or chronic pancreatitis (n = 20) and in healthy controls (n = 48). Quantitative enzyme-linked immunosorbent assays and multiplex protein arrays were used to determine circulating levels of VEGF, VEGFR-1, PlGF, PDGF-AA, PDGF-BB, Ang-1 and EGF. Multivariate analyses on cancer-specific survival were performed with a Cox proportional hazards model.
  
  
  RESULTS
  VEGF (p < 0.0001), PDGF-AA (p < 0.0001), Ang-1 (p = 0.002) and EGF (p < 0.0001) were differentially expressed in patients with pancreatic cancer compared to healthy controls. The presence of lymph node metastases was associated with increased levels of all CAC except for PlGF, whereas there were only minor associations of CAC with other clinicopathologic variables. The multivariate model including the entire angiogenic panel revealed high levels of circulating PDGF-AA (hazard ratio 4.58; 95% confidence interval 1.43 - 14.69) as predictor of poor cancer-specific survival, whereas high levels of PDGF-BB (0.15; 0.15 - 0.88), Ang-1 (0.30; 0.10 - 0.93) and VEGF (0.24; 0.09 - 0.57) were associated with a favorable prognosis.
  
  
  CONCLUSIONS
  Circulating levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer, if a panel of several CAC is considered simultaneously. These data should be considered in future studies evaluating angiogenic factors as prognostic biomarkers and therapeutic targets in patients with pancreatic cancer.
authors: Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
authors: Nuh N
authors: NN
authors: Rahbari
authors: Thomas
authors: T
authors: Schmidt
authors: Christine S
authors: CS
authors: Falk
authors: Ulf
authors: U
authors: Hinz
authors: Magdalene
authors: M
authors: Herber
authors: Ulrich
authors: U
authors: Bork
authors: Markus W
authors: MW
authors: Büchler
authors: Jürgen
authors: J
authors: Weitz
authors: Moritz
authors: M
authors: Koch
mesh_terms: D000368:Aged; D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D000803:Angiotensin I / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D000077214:Becaplermin; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics
chemical_list: D042501:Angiogenic Proteins; D016207:Cytokines; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C098069:PIGF protein, human; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D000803:Angiotensin I; D040281:Vascular Endothelial Growth Factor Receptor-1