An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer.
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.
Weichselbaum
Ralph R
RR
Department of Radiation and Cellular Oncology, Ludwig Center for Metastasis Research, Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
Ishwaran
Hemant
H
Yoon
Taewon
T
Nuyten
Dimitry S A
DS
Baker
Samuel W
SW
Khodarev
Nikolai
N
Su
Andy W
AW
Shaikh
Arif Y
AY
Roach
Paul
P
Kreike
Bas
B
Roizman
Bernard
B
Bergh
Jonas
J
Pawitan
Yudi
Y
van de Vijver
Marc J
MJ
Minn
Andy J
AJ
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
D000970:Antineoplastic Agents; D015415:Biomarkers; D007372:Interferons