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.

Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer

“…Finally, we found no association between the rs1126772, rs11730582, and rs4754 SNPs, as well as their haplotypes and pretreatment circulating OPN levels in our NSCLC cohort. Similar results were previously obtained by several other authors in lung cancer and melanoma patients [9,10,61]. However, rs11730582 in the promoter region was shown to be linked to serum/plasma OPN levels in nasopharyngeal and breast cancers [48,49].…”

The Role of Osteopontin Expression in the Prognosis of Malignant Melanoma

“…Interferon-α stimulated anti-melanoma cytotoxic T lymphocytes by increasing the Th1 response rate, while OPN affects Th1 cells by increasing IFN-α production. In the IFN melanoma study, although the survival of the cases with a high level of OPN and receiving interferon treatment was better, no statistical significance could be demonstrated [18].…”

Increased Circulating Osteopontin Levels Promote Primary Tumour Growth, but Do Not Induce Metastasis in Melanoma

“…In addition, transcriptomic analyses have revealed that OPN is one of the most highly upregulated proteins in metastatic melanoma compared to benign nevi [ 67 ]. Furthermore, the levels of OPN are also elevated in the blood of melanoma patients compared to healthy controls [ 46 , 47 , 68 ].…”

“…One report found a correlation between high OPN expression in tumours and increased risk of lymph node metastasis, as well as a marginal decrease in survival, which is closely linked to distant metastasis formation [ 71 ]. By contrast, a separate study found no correlation between OPN expression and overall or recurrence-free survival in melanoma patients [ 68 ].…”