title: An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer.
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.
authors.affiliation: Department of Radiation and Cellular Oncology, Ludwig Center for Metastasis Research, Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: Hemant
authors.initials: H
authors.lastname: Ishwaran
authors.forename: Taewon
authors.initials: T
authors.lastname: Yoon
authors.forename: Dimitry S A
authors.initials: DS
authors.lastname: Nuyten
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Baker
authors.forename: Nikolai
authors.initials: N
authors.lastname: Khodarev
authors.forename: Andy W
authors.initials: AW
authors.lastname: Su
authors.forename: Arif Y
authors.initials: AY
authors.lastname: Shaikh
authors.forename: Paul
authors.initials: P
authors.lastname: Roach
authors.forename: Bas
authors.initials: B
authors.lastname: Kreike
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
authors.forename: Andy J
authors.initials: AJ
authors.lastname: Minn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D004249:DNA Damage / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000502:physiology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007372:Interferons