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Analysis of surrogate gene expression markers in peripheral blood of melanoma patients to predict treatment outcome of adjuvant pegylated interferon alpha 2b (EORTC 18991 side study)

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Abstract

We analysed mRNA levels of interferon response genes (ISG15, STAT1, CXCL10) of inhibitors of the JAK/STAT pathway (STAT3, SOCS1, SOCS3) and of cytokines (TNFα, IL10, TGFß1) in peripheral blood of 91 stage III melanoma patients enrolled in EORTC 18991 trial to find biomarkers indicative for disease stage and predictive for efficacy of pegylated interferon alpha-2b (PEG-IFNα-2b) therapy. mRNA levels were analysed at baseline and after 6 months. Univariate and multivariate analyses were performed to estimate the prognostic and predictive role of mRNA levels for distant metastasis-free survival (DMFS) and relapse-free survival (RFS). Compared to healthy controls, melanoma patients showed significantly higher TGFβ1 mRNA levels. In a multivariate model, increasing SOCS1 and SOCS3 mRNA levels were associated with worse RFS (P = 0.02 and P = 0.04, respectively) and DMFS (P = 0.05 and P = 0.05, respectively) due to negative correlation between, respectively, SOCS1/SOCS3 mRNA levels and ulceration or Breslow thickness. No impact of PEG-IFNα-2b on mRNA levels was observed except for ISG15 mRNA levels, which decreased in the treatment arm (P = 0.001). It seems that patients with a decrease >60 % of ISG15 mRNA levels during 6 months PEG-IFNα-2b had inferior outcome.

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Abbreviations

PEG-IFNα-2b:

Pegylated interferon alpha-2b

SOCS:

Suppressors of cytokine signalling

DMFS:

Metastasis-free survival

RFS:

Relapse-free survival

pB:

Peripheral blood

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Acknowledgments

This study was supported by Sonnenfeld Stiftung from Germany, Berliner Krebsgesellschaft from Germany, and Fonds Cancer (FOCA) from Belgium.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Medicine III, Charité-CBF, Hindenburgdamm 30, 12200, Berlin, Germany

    Antonia Busse, Alberto Fusi, Anika Nonnenmacher & Ulrich Keilholz

  2. European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium

    Jérôme Rapion & Stefan Suciu

  3. Istituto Nazionale dei Tumori, Milan, Italy

    Mario Santinami

  4. Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

    Wim H. J. Kruit & Alexander M. M. Eggermont

  5. Istituto Europeo di Oncologia, Milan, Italy

    Alessandro Testori

  6. Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Cornelis J. A. Punt

  7. St. Georges Hospital, London, UK

    Angus G. Dalgleish

  8. Jewish General Hospital, Montreal, Canada

    Alan Spatz

  9. Cancer Institute Gustave Roussy, Villejuif-Paris, France

    Alexander M. M. Eggermont

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  1. Antonia Busse
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Correspondence to Antonia Busse.

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Busse, A., Rapion, J., Fusi, A. et al. Analysis of surrogate gene expression markers in peripheral blood of melanoma patients to predict treatment outcome of adjuvant pegylated interferon alpha 2b (EORTC 18991 side study). Cancer Immunol Immunother 62, 1223–1233 (2013). https://doi.org/10.1007/s00262-013-1428-4

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