An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer

Ralph R. Weichselbaum, Hemant Ishwaran, Taewon Yoon, Dimitry S.A. Nuyten, Samuel W. Baker, Nikolai Khodarev, Andy W. Su, Arif Y. Shaikh, Paul Roach, Bas Kreike, Bernard Roizman, Jonas Bergh, Yudi Pawitan, Marc J. Van De Vijver, Andy J. Minn

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272 Scopus citations

Abstract

Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.

Original languageEnglish (US)
Pages (from-to)18490-18495
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number47
DOIs
StatePublished - Nov 25 2008

ASJC Scopus subject areas

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    Weichselbaum, R. R., Ishwaran, H., Yoon, T., Nuyten, D. S. A., Baker, S. W., Khodarev, N., Su, A. W., Shaikh, A. Y., Roach, P., Kreike, B., Roizman, B., Bergh, J., Pawitan, Y., Van De Vijver, M. J., & Minn, A. J. (2008). An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 105(47), 18490-18495. https://doi.org/10.1073/pnas.0809242105