title: Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer.
abstract: Pancreatic cancer consists of a heterogenous bulk of tumor cells and stroma cells which contribute to tumor progression by releasing angiogenic factors. Those factors can be detected as circulating serum factors. We performed a compartment-specific analysis of tumor-derived and stroma-derived angiogenic factors to identify biomarkers and molecular targets for the treatment of pancreatic cancer. Kryo-frozen tissue from primary ductal adenocarcinomas (n = 51) was laser-microdissected to isolate tumor and stroma tissue. Expression of 17 angiogenic factors (angiopoietin-2, follistatin, GCSF, HGF, interleukin-8, leptin, PDGF-BB, PECAM-1, VEGF, matrix metalloproteinase -1, -2, -3, -7, -9, -10, -12, and -13) was analyzed using a multiplex elisa assay for tissue-derived proteins and corresponding serum. Our study reveals a compartment-specific expression profile for several angiogenic factors and matrix metalloproteinases. ROC analysis of corresponding serum samples reveals MMP-7 and MMP-12 as strong classifiers for the diagnosis of patients with pancreatic cancer vs. healthy control donors. High expression of tumor-derived PDGF-BB and MMP-1 correlates with prolonged survival in univariate and multivariate analysis. In conclusion, a distinct expression patterns for angiogenic cytokines and MMPs in pancreatic cancer and surrounding stroma may implicate them as novel targets for cancer treatment. Tumor-derived PDGF-BB and MMP-1 are significant and independent prognostic markers for poor survival.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahlert
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Fiala
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Musso
authors.affiliation: Medical Oncology, National Center for Tumor Diseases and Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Halama
authors.affiliation: Medical Oncology, National Center for Tumor Diseases and Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Keim
authors.affiliation: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven 3000, Belgium. Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, Department of Oncology, KU, Leuven 3000, Belgium.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mazzone
authors.affiliation: Institute of Pathology, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Pecqueux
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Fee
authors.initials: F
authors.lastname: Klupp
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany.
authors.forename: Nuh
authors.initials: N
authors.lastname: Rahbari
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schölch
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pilarsky
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Weitz
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines