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

doi:10.1007/s00262-013-1428-4

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 journal › Article › peer-review

7 Citations (Scopus)

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 language	English
Pages (from-to)	1223-1233
Number of pages	11
Journal	Cancer Immunology, Immunotherapy
Volume	62
Issue number	7
DOIs	https://doi.org/10.1007/s00262-013-1428-4
Publication status	Published - Jul 2013
Externally published	Yes

Keywords

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

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10.1007/s00262-013-1428-4

Cite this

Busse, A., Rapion, J., Fusi, A., Suciu, S., Nonnenmacher, A., Santinami, M., Kruit, W. H. J., Testori, A., Punt, C. J. A., Dalgleish, A. G., Spatz, A., Eggermont, A. M. M., & Keilholz, U. (2013). 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 Immunology, Immunotherapy, 62(7), 1223-1233. https://doi.org/10.1007/s00262-013-1428-4

@article{e3d6327247d14924bee18e526cd2ebe9,

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, TGF{\ss}1) 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.",

keywords = "Adjuvant pegylated interferon alpha-2b, EORTC, Immunosuppressive cytokines, Interferon response genes, Melanoma, RT-PCR",

author = "Antonia Busse and J{\'e}r{\^o}me Rapion and Alberto Fusi and Stefan Suciu and Anika Nonnenmacher and Mario Santinami and Kruit, \{Wim H.J.\} and Alessandro Testori and Punt, \{Cornelis J.A.\} and Dalgleish, \{Angus G.\} and Alan Spatz and Eggermont, \{Alexander M.M.\} and Ulrich Keilholz",

note = "Funding Information: Acknowledgments This study was supported by Sonnenfeld Stif-tung from Germany, Berliner Krebsgesellschaft from Germany, and Fonds Cancer (FOCA) from Belgium.",

year = "2013",

month = jul,

doi = "10.1007/s00262-013-1428-4",

language = "English",

volume = "62",

pages = "1223--1233",

journal = "Cancer Immunology, Immunotherapy",

issn = "0340-7004",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "7",

}

Busse, A, Rapion, J, Fusi, A, Suciu, S, Nonnenmacher, A, Santinami, M, Kruit, WHJ, Testori, A, Punt, CJA, Dalgleish, AG, Spatz, A, Eggermont, AMM & Keilholz, U 2013, '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 Immunology, Immunotherapy, vol. 62, no. 7, pp. 1223-1233. https://doi.org/10.1007/s00262-013-1428-4

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). / Busse, Antonia; Rapion, Jérôme; Fusi, Alberto et al.
In: Cancer Immunology, Immunotherapy, Vol. 62, No. 7, 07.2013, p. 1223-1233.

Research output: Contribution to journal › Article › peer-review

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 - https://www.scopus.com/pages/publications/84879551963

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 -

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

Keywords

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