Postoperative course and prognostic value of circulating angiogenic cytokines after pancreatic cancer resection
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Cui Yang1, Ulrich Bork1, Sebastian Schölch1, Yakup Kulu2, Lars Kaderali3, Uta L. Bolstorff1, Christoph Kahlert1, Jürgen Weitz1, Nuh N. Rahbari1 and Christoph Reissfelder1
1Department of Gastrointestinal, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
2Department of General, Gastrointestinal and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
3Institute of Bioinformatics, University of Greifswald, Greifswald, Germany
Christoph Reissfelder, email: [email protected]
Keywords: pancreatic cancer, circulating cytokines, postoperative, VEGF, TNF-α
Received: May 23, 2017 Accepted: July 31, 2017 Published: August 17, 2017
Background: Circulating angiogenic cytokines (CACs) have been confirmed as prognostic biomarkers and therapeutic targets in several solid tumors. However, their role as prognostic biomarkers in resected pancreatic ductal adenocarcinoma (PDAC) is unknown.
Results: The expression of CACs in patients with PDAC differs from those with CP both pre- and postoperatively. Correlation analyses show significant correlations between circulating levels of CACs: VEGF was correlated with IL-6 (r = 0.457), FGF (r = 0.44), G-CSF (r = 0.543), HGF (r = 0.586) and SDF-1α (r = 0.784) before the surgery. The circulating levels of TNF-α correlated with the serum concentration of IL-4 before (r= 0.656) and after the resection (r = 0.776 on POD 3, r = 0.865 on POD 7). Gender did not show any correlation with serum levels of CAC, except for significantly higher levels of EGF in males (P = 0.002). Other clinicopathological variables such as age (< 65 vs. > 65 years), T, N, or UICC stage did not have an association with the cytokine levels. The multivariate model including the entire angiogenic panel revealed that postoperative increasing levels of EGF (P = 0.023), PDGFA-A (P = 0.024), TNF-α (P = 0.001) and IL-8 (P = 0.049) were associated with a favorable prognosis, whereas elevating levels of VEGF (P = 0.005) correlated with a poor cancer-specific survival.
Materials and Methods: Preoperative and postoperative blood samples were collected in patients undergoing surgery for PDAC (n = 40) or chronic pancreatitis (CP; n = 9). Serum levels of 13 angiogenic cytokines (IL-4, IL-6, FGF-b, G-CSF, TNF-α, VEGF, HGF, SDF-1α, IL-8, EGF, Ang-1, PDGF-AA and PlGF) were analyzed using ELISA and Multiplex. Prognostic factors were identified by a Cox proportional hazards model.
Conclusions: Postoperative changes of serum levels of certain angiogenic cytokines correlate with patients’ prognosis after resection for pancreatic cancer. CACs should thus be considered as biomarkers in patients with resected pancreatic cancer.
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