Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer
// Maria Thomsen 1, 2 , Christian Kersten 3 , Halfdan Sorbye 4 , Eva Skovlund 5 , Bengt Glimelius 6 , Per Pfeiffer 7 , Julia S. Johansen 8 , Elin H. Kure 9 , Tone Ikdahl 10 , Kjell Magne Tveit 1, 2, 11 , Thoralf Christoffersen 12 , Tormod Kyrre Guren 1, 11 1 Department of Oncology, Oslo University Hospital, Oslo, Norway 2 Institute of Clinical Medicine, University of Oslo, Oslo, Norway 3 Department of Oncology, Southern Hospital Trust, Kristiansand, Norway 4 Department of Oncology, Haukeland University Hospital, University of Bergen, Bergen, Norway 5 Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway 6 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden 7 Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark 8 Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark 9 Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway 10 Akershus University Hospital, Nordbyhagen, Norway 11 K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, Oslo, Norway 12 Department of Pharmacology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Correspondence to: Maria Thomsen, email: uxthmg@ous-hf.no Keywords: mCRC, IL-6, CRP, prognostic biomarker, survival Received: May 20, 2016 Accepted: September 19, 2016 Published: October 12, 2016 ABSTRACT 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.