Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer
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Author
Kahlert, Christoph
Fiala, Maria
Musso, Gabriel
Halama, Niels
Keim, Sophia
Mazzone, Massimiliano
Lasitschka, Felix
Pecqueux, Mathieu
Klupp, Fee
Schmidt, Thomas
Rahbari, Nuh
Schölch, Sebastian
Pilarsky, Christian
Ulrich, Alexis
Schneider, Martin
Weitz, Juergen
Koch, Moritz
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.18632/oncotarget.2651Metadata
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Kahlert, C., M. Fiala, G. Musso, N. Halama, S. Keim, M. Mazzone, F. Lasitschka, et al. 2014. “Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer.” Oncotarget 5 (24): 12978-12989.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350362/pdf/Terms of Use
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