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Cancer Immunology, Immunotherapy

, Volume 64, Issue 6, pp 769–776 | Cite as

Evaluation of serum osteopontin level and gene polymorphism as biomarkers: analyses from the Nordic Adjuvant Interferon alpha Melanoma trial

  • Lina PrasmickaiteEmail author
  • Gisle Berge
  • Ingrid J. Bettum
  • Steinar Aamdal
  • Johan Hansson
  • Lars Bastholt
  • Miriam Øijordsbakken
  • Kjetil Boye
  • Gunhild M. Mælandsmo
Original Article

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.

Keywords

Melanoma Osteopontin Interferon Gene polymorphism Serum biomarker 

Abbreviations

AJCC

American Joint Committee on Cancer

ELISA

Enzyme-linked immunosorbent assay

IFN-α

Interferon alpha

MMP

Matrix metalloproteinase

OPN

Osteopontin

OS

Overall survival

RFS

Relapse-free survival

SIBLING

Small integrin-binding ligand N-linked glycoprotein

SNP

Single-nucleotide polymorphism

Notes

Acknowledgments

The project was supported by the Norwegian Cancer Society, the Research Council of Norway and the South East Regional Health Authority. We thank Karen-Marie Heintz and Geir Frode Øy from the genotyping core facility for performing SNP analysis.

Conflict of interest

Johan Hansson and Lars Bastholt have been involved in advisory board activities for Merck MSD. Lars Bastholt has received congress-related travel support from Merck MSD. The other authors have no conflicts of interest to report.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Lina Prasmickaite
    • 1
    Email author
  • Gisle Berge
    • 1
  • Ingrid J. Bettum
    • 1
  • Steinar Aamdal
    • 2
    • 3
  • Johan Hansson
    • 4
  • Lars Bastholt
    • 5
  • Miriam Øijordsbakken
    • 6
  • Kjetil Boye
    • 1
    • 7
  • Gunhild M. Mælandsmo
    • 1
    • 8
    • 9
  1. 1.Division of Cancer, Surgery and Transplantation, Department of Tumor Biology, Institute for Cancer ResearchOslo University HospitalMontebello, OsloNorway
  2. 2.Section for Clinical Cancer Research and Resource DevelopmentOslo University HospitalOsloNorway
  3. 3.Faculty of MedicineUniversity of OsloOsloNorway
  4. 4.Department of Oncology-PathologyKarolinska InstitutetStockholmSweden
  5. 5.Department of OncologyOdense University HospitalOdenseDenmark
  6. 6.Department of Medical BiochemistryOslo University HospitalOsloNorway
  7. 7.Department of OncologyOslo University HospitalOsloNorway
  8. 8.Institute for Pharmacy, Faculty of Health ScienceUniversity of TromsøTromsøNorway
  9. 9.K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of MedicineUniversity of OsloOsloNorway

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