title: Non-small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease.
abstract: Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD. Unsupervised hierarchical clustering and non-parametric analyses were performed. False discovery rate was used to adjust for multiple testing. Clustering of cytokine and MMP concentrations in the serum revealed a distinct separation of the NSCLC patients from the COPD group. Individual concentrations of thymus and activation-regulated cytokine (C-C motif chemokine ligand 17), Gro-b (C-X-C motif chemokine ligand 2 (CXCL2)), CXCL13, interleukin (IL)-1ra, IL-6, IL-8 (CXCL8), IL-16, IL-17A, macrophage migration inhibitory factor (MIF), granulocyte colony-stimulating factor, platelet-derived growth factor subunit B, MMP-2, MMP-8 and MMP-12 were significantly different in serum from NSCLC and COPD patients. Moreover, the interferon-γ/IL-10 ratio was lower in cancer patients compared with COPD patients, consistent with a cytokine milieu favouring tumour tolerance. Our results suggest that NSCLC is characterised by a distinct inflammatory signature in serum. The different cytokine profiles in NSCLC and COPD patients may represent tumour-promoting and tumour-suppressing immune responses developing in response to mucosal inflammation and mutations induced by smoking.
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital , Oslo, Norway.
authors.forename: Hanne Astrid
authors.initials: HA
authors.lastname: Eide
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital , Oslo, Norway.
authors.forename: Ann Rita
authors.initials: AR
authors.lastname: Halvorsen
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital , Oslo, Norway.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sandhu
authors.affiliation: Department for Cell Therapy, Oslo University Hospital-The Norwegian Radium Hospital , Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Fåne
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department of Medicine, Vestfold Hospital Trust, Tønsberg, Norway.
authors.forename: Janna
authors.initials: J
authors.lastname: Berg
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital , Oslo, Norway.
authors.forename: Vilde Drageset
authors.initials: VD
authors.lastname: Haakensen
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department for Environmental Health and Science, Telemark University College, Bø in Telemark, Norway.
authors.forename: Elin H
authors.initials: EH
authors.lastname: Kure
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Odd Terje
authors.initials: OT
authors.lastname: Brustugun
authors.affiliation: Department of Oncology, National Advisory Unit on Late Effects After Cancer Treatment, Oslo University Hospital-The Norwegian Radium Hospital , Oslo, Norway.
authors.forename: Cecilie Essholt
authors.initials: CE
authors.lastname: Kiserud
authors.affiliation: Department for Cell Therapy, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Jon Amund
authors.initials: JA
authors.lastname: Kyte
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Åslaug
authors.initials: Å
authors.lastname: Helland