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Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer

Title: Prognostic impact of a compartment-specific angiogenic marker profile in patients with pancreatic cancer
Authors: Kahlert, Christoph; Fiala, Maria; Musso, Gabriel; Halama, Niels; Keim, Sophia; Mazzone, Max; Lasitschka, Felix; Pecqueux, Mathieu; Klupp, Fee; Schmidt, Thomas; Rahbari, Nuh; Schölch, Sebastian; Pilarsky, Christian; Ulrich, Alexis; Schneider, Martin; Weitz, Juergen; Koch, Moritz
Source: ISSN:1949-2553 ; Oncotarget, vol. 5 (24), (12978-89.
Publisher Information: Impact Journals
Publication Year: 2014
Subject Terms: Aged; Biomarkers; Tumor; Cohort Studies; Cytokines; Female; Humans; Male; Neovascularization; Pathologic; Pancreatic Neoplasms; Prognosis; Science & Technology; Life Sciences & Biomedicine; Oncology; Cell Biology; Pancreatic cancer; stroma; angiogenic cytokines; expression profile; PHASE-III TRIAL; DUCTAL ADENOCARCINOMA; MATRIX METALLOPROTEINASES; INVASION FRONT; SURVIVAL; EXPRESSION; GEMCITABINE; METASTASIS; CARCINOMA; 1112 Oncology and Carcinogenesis
Description: 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. ; status: Published
Document Type: article in journal/newspaper
Language: English
Relation: https://lirias.kuleuven.be/handle/123456789/668071; https://doi.org/10.18632/oncotarget.2651; https://pubmed.ncbi.nlm.nih.gov/25483099
DOI: 10.18632/oncotarget.2651
Availability: https://lirias.kuleuven.be/handle/123456789/668071; https://doi.org/10.18632/oncotarget.2651; https://pubmed.ncbi.nlm.nih.gov/25483099
Rights: info:eu-repo/semantics/restrictedAccess ; intranet
Accession Number: edsbas.1759DF72
Database: BASE