title: Evaluation of serum osteopontin level and gene polymorphism as biomarkers: analyses from the Nordic Adjuvant Interferon alpha Melanoma trial.
abstract: Malignant melanoma is highly aggressive cancer with poor prognosis and few therapeutic options. Interferon alpha (IFN-α) has been tested as adjuvant immunotherapy in high-risk melanoma patients in a number of studies, but its beneficial role is controversial. Although IFN-α treatment can prolong relapse-free survival, the effect on overall survival is not significant. However, a small subset of patients benefits from the treatment, signifying the need for biomarkers able to identify a responding subgroup. Here we evaluated whether serum osteopontin (OPN) could function as a biomarker identifying patients with poor prognosis that might benefit from IFN-α. The choice of osteopontin was based on the knowledge about the dual role of this protein in cancer and immune response, an apparent association between OPN and IFN signaling and a prognostic value of OPN in multiple other tumor types. Serum samples from 275 high-risk melanoma patients enrolled in the Nordic Adjuvant IFN Melanoma trial were analyzed for circulating OPN concentrations and OPN promoter polymorphisms in position -443. The potential relation between serum OPN levels, the genotypes and survival in non-treated patients and patients receiving adjuvant IFN-α was investigated. Although slightly better survival was observed in the treated patients that had high levels of OPN, the difference was not statistically significant. In conclusion, serum OPN (its level or the genotype) cannot distinguish melanoma patients with poor prognosis, or patients that might benefit from adjuvant treatment with IFN-α.
authors.affiliation: Division of Cancer, Surgery and Transplantation, Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0310, Montebello, Oslo, Norway, linap@rr-research.no.
authors.forename: Lina
authors.initials: L
authors.lastname: Prasmickaite
authors.forename: Gisle
authors.initials: G
authors.lastname: Berge
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Bettum
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
authors.forename: Miriam
authors.initials: M
authors.lastname: Øijordsbakken
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053495:Osteopontin / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D016898:Interferon-alpha; D053495:Osteopontin
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