Abstract
Interferon alpha (IFNα) is approved for adjuvant treatment of stage III melanoma in Europe and the US. Its clinical efficacy, however, is restricted to a subpopulation of patients while side effects occur in most of treated patients. Thus, the identification of predictive biomarkers would be highly beneficial to improve the benefit to risk ratio. In this regard, STAT3 is important for signaling of the IFNα receptor. Moreover, the STAT3 single-nucleotide polymorphism (SNP) rs4796793 has recently been reported to be associated with IFNα sensitivity in metastatic renal cell carcinoma. To translate this notion to melanoma, we scrutinized the impact of rs4796793 functionally and clinically in this cancer. Interestingly, melanoma cells carrying the minor allele of rs4796793 were the most sensitive to IFNα in vitro. However, we did not detect a correlation between SNP genotype and STAT3 mRNA expression for either melanoma cells or for peripheral blood lymphocytes. Next, we analyzed the impact of rs4796793 on the clinical outcome of 259 stage III melanoma patients of which one-third had received adjuvant IFNα treatment. These analyses did not reveal a significant association between the STAT3 rs4796793 SNP and patients’ progression free or overall survival when IFNα treated and untreated patients were compared. In conclusion, STAT3 rs4796793 SNP is no predictive marker for the efficacy of adjuvant IFNα treatment in melanoma patients.
Highlights
Malignant melanoma is an aggressive skin cancer originating from melanocytes
While early-stage melanoma can be cured in most cases by surgical excision of the tumor, already for patients with loco-regional disease beyond the primary tumor the Abbreviations: IFNα, interferon alpha; PBL, peripheral blood lymphocytes; STAT3, signal transducer and activator of transcription 3; SNP, single-nucleotide polymorphism
As expected from the role of STAT3 for lymphocytes, its expression was significantly higher in PBLs than in the melanoma cell lines (p < 0.0001; Kruskal–Wallis)
Summary
Malignant melanoma is an aggressive skin cancer originating from melanocytes. In the US, melanoma is one of the few common cancers with increasing incidence rates over the last decade, i.e., a 2.4% increase per year among white women and 2.1% among white men during 1999–2009 (1). The economic burden of this disease is reflected by the recent report that an individual in the US loses on average 20.4 years of their potential lifetime as a result of melanoma mortality compared with 16.6 years for all other malignant cancers (3). The prognosis of a melanoma patient is largely dependent on the stage of disease. While early-stage melanoma can be cured in most cases by surgical excision of the tumor, already for patients with loco-regional disease beyond the primary tumor the Abbreviations: IFNα, interferon alpha; PBL, peripheral blood lymphocytes; STAT3, signal transducer and activator of transcription 3; SNP, single-nucleotide polymorphism
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