title: Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma.
abstract: Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients with metastatic melanoma. IL-6 was measured by ELISA in serum samples from 103 patients with metastatic melanoma obtained before IL-2-based immunotherapy. Patients with metastatic melanoma had higher serum IL-6 than healthy individuals (median 3.4 ng/l, range 0.3-93 ng/l vs. median 1.4 ng/l, range 0.25-22.5 ng/l, P<0.0001). Pretreatment serum IL-6 was elevated in 43% of the patients. Patients with elevated pretreatment serum IL-6 had shorter overall survival (OS) compared with patients with normal serum IL-6 (P<0.0002). The median OS was 10.8 months [95% confidence interval (CI): 8.86-13.46] in patients with normal serum IL-6 compared with 4.5 months (95% CI: 3.04-7.39) in patients with elevated serum IL-6. Multivariate Cox analysis showed that serum IL-6 [hazard ratio (HR)=1.82, 95% CI: 1.19-2.78, P=0.006] and serum lactate dehydrogenase (HR=2.02, 95% CI: 1.31-3.11, P=0.001) were independent prognostic biomarkers of OS. A combination variable of elevated serum IL-6 and elevated serum lactate dehydrogenase almost quadrupled the risk of early death (HR=3.67, 95% CI: 2.17-6.20, P<0.0001) compared with patients with normal serum levels of these two biomarkers. Elevated serum IL-6 is an independent prognostic biomarker of short OS in patients with metastatic melanoma. A larger retrospective study is ongoing to confirm the findings. To validate serum IL-6 further as a prognostic biomarker, a prospective study is required.
authors.affiliation: Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. lise.hoejberg@ouh.regionsyddanmark.dk
authors.forename: Lise
authors.initials: L
authors.lastname: Hoejberg
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Julie
authors.initials: J
authors.lastname: Gehl
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000201:enzymology / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood* / Q000201:enzymology / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6; D007770:L-Lactate Dehydrogenase