Interleukin-6 and C-reactive Protein as Prognostic Biomarkers in Metastatic Colorectal Cancer

Oncotarget. 2016 Nov 15;7(46):75013-75022. doi: 10.18632/oncotarget.12601.

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.

Keywords: CRP; IL-6; mCRC; prognostic biomarker; survival.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • C-Reactive Protein*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / therapy
  • Combined Modality Therapy
  • Female
  • Genes, ras
  • Humans
  • Inflammation Mediators
  • Interleukin-6 / blood*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Inflammation Mediators
  • Interleukin-6
  • C-Reactive Protein
  • Proto-Oncogene Proteins B-raf