title: 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).
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.
authors.affiliation: Department of Medicine III, Charité-CBF, Hindenburgdamm 30, 12200, Berlin, Germany. antonia.busse@charite.de
authors.forename: Antonia
authors.initials: A
authors.lastname: Busse
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rapion
authors.forename: Alberto
authors.initials: A
authors.lastname: Fusi
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Anika
authors.initials: A
authors.lastname: Nonnenmacher
authors.forename: Mario
authors.initials: M
authors.lastname: Santinami
authors.forename: Wim H J
authors.initials: WH
authors.lastname: Kruit
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Angus G
authors.initials: AG
authors.lastname: Dalgleish
authors.forename: Alan
authors.initials: A
authors.lastname: Spatz
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b