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)

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1223-1233
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume62
Issue number7
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Adjuvant pegylated interferon alpha-2b
  • EORTC
  • Immunosuppressive cytokines
  • Interferon response genes
  • Melanoma
  • RT-PCR

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

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