Clinical Research Papers:
Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer
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Christoph Kahlert1,*, Maria Fiala1,*, Gabriel Musso2,3, Niels Halama4, Sophia Keim4, Massimiliano Mazzone5,6, Felix Lasitschka7, Mathieu Pecqueux8, Fee Klupp1, Thomas Schmidt1, Nuh Rahbari8, Sebastian Schölch8, Christian Pilarsky8, Alexis Ulrich1, Martin Schneider1, Juergen Weitz8, Moritz Koch8
1Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg 69120, Germany
2Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
3Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA 02115, USA
4Medical Oncology, National Center for Tumor Diseases and Hamamatsu Tissue Imaging and Analysis (TIGA) Center, Institute for Medical Biometry and Informatics, University of Heidelberg, Germany
5Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven 3000, Belgium
6Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, Department of Oncology, KU, Leuven 3000, Belgium
7Institute of Pathology, University of Heidelberg, Heidelberg 69120, Germany
8Department of General, Visceral and Thoracic Surgery, University of Dresden, Dresden 01307, Germany
*These authors contributed equally to this work
Christoph Kahlert, e-mail: firstname.lastname@example.org
Keywords: Pancreatic cancer, stroma, angiogenic cytokines, expression profile
Received: August 05, 2014 Accepted: October 27, 2014 Published: December 30, 2014
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.
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