Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer
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Maria Thomsen1,2, Christian Kersten3, Halfdan Sorbye4, Eva Skovlund5, Bengt Glimelius6, Per Pfeiffer7, Julia S. Johansen8, Elin H. Kure9, Tone Ikdahl10, Kjell Magne Tveit1,2,11, Thoralf Christoffersen12, Tormod Kyrre Guren1,11
1Department of Oncology, Oslo University Hospital, Oslo, Norway
2Institute of Clinical Medicine, University of Oslo, Oslo, Norway
3Department of Oncology, Southern Hospital Trust, Kristiansand, Norway
4Department of Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway
5Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway
6Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
7Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
8Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
9Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
10Akershus University Hospital, Nordbyhagen, Norway
11K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway
12Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Maria Thomsen, email: [email protected]
Keywords: mCRC, IL-6, CRP, prognostic biomarker, survival
Received: May 20, 2016 Accepted: September 19, 2016 Published: October 12, 2016
Objectives: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status.
Results: High levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.0 versus 16.6 months, respectively (P < 0.001). Stratified according to increasing CRP levels, median OS varied from 24.3 months to 12.3 months, (P < 0.001). IL-6 and CRP levels affected overall prognosis also in adjusted analyses. The effect of IL-6 was particularly pronounced in patients with BRAF mutation (interaction P = 0.004).
Materials and Methods: IL-6 and CRP were determined in pre-treatment serum samples from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progression-free survival (PFS) and overall survival (OS) was estimated.
Conclusions: High baseline serum consentrations of IL-6 or CRP were associated with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status.
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