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01.07.2013 | Original Article

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)

verfasst von: Antonia Busse, Jérôme Rapion, Alberto Fusi, Stefan Suciu, Anika Nonnenmacher, Mario Santinami, Wim H. J. Kruit, Alessandro Testori, Cornelis J. A. Punt, Angus G. Dalgleish, Alan Spatz, Alexander M. M. Eggermont, Ulrich Keilholz

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2013

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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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Titel: 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)
verfasst von: Antonia Busse
Jérôme Rapion
Alberto Fusi
Stefan Suciu
Anika Nonnenmacher
Mario Santinami
Wim H. J. Kruit
Alessandro Testori
Cornelis J. A. Punt
Angus G. Dalgleish
Alan Spatz
Alexander M. M. Eggermont
Ulrich Keilholz
Publikationsdatum: 01.07.2013
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2013
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-013-1428-4

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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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