TY - JOUR
T1 - 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)
AU - Busse, Antonia
AU - Rapion, Jérôme
AU - Fusi, Alberto
AU - Suciu, Stefan
AU - Nonnenmacher, Anika
AU - Santinami, Mario
AU - Kruit, Wim H.J.
AU - Testori, Alessandro
AU - Punt, Cornelis J.A.
AU - Dalgleish, Angus G.
AU - Spatz, Alan
AU - Eggermont, Alexander M.M.
AU - Keilholz, Ulrich
N1 - Funding Information:
Acknowledgments This study was supported by Sonnenfeld Stif-tung from Germany, Berliner Krebsgesellschaft from Germany, and Fonds Cancer (FOCA) from Belgium.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - Adjuvant pegylated interferon alpha-2b
KW - EORTC
KW - Immunosuppressive cytokines
KW - Interferon response genes
KW - Melanoma
KW - RT-PCR
UR - http://www.scopus.com/inward/record.url?scp=84879551963&partnerID=8YFLogxK
U2 - 10.1007/s00262-013-1428-4
DO - 10.1007/s00262-013-1428-4
M3 - Article
C2 - 23624802
AN - SCOPUS:84879551963
SN - 0340-7004
VL - 62
SP - 1223
EP - 1233
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 7
ER -