An Interferon-related Gene Signature for DNA Damage Resistance is a Predictive Marker for Chemotherapy and Radiation for Breast Cancer

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Nov 13

PMID 19001271

Citations 337

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Interferon-driven Metabolic Reprogramming and Tumor Microenvironment Remodeling.

Chang T, Ho P Immune Netw. 2025; 25(1):e8.

PMID: 40078784 PMC: 11896656. DOI: 10.4110/in.2025.25.e8.

Loss of JAK1 Function Causes G2/M Cell Cycle Defects Vulnerable to Kif18a Inhibition.

Kelley V, Baro M, Gasperi W, Ader N, Lea H, Lee H bioRxiv. 2025; .

PMID: 40060568 PMC: 11888196. DOI: 10.1101/2025.02.19.638911.

Impact of developmental state, p53 status, and interferon signaling on glioblastoma cell response to radiation and temozolomide treatment.

Berezovsky A, Nuga O, Datta I, Bergman K, Sabedot T, Gurdziel K PLoS One. 2025; 20(2):e0315171.

PMID: 39919036 PMC: 11805374. DOI: 10.1371/journal.pone.0315171.

Ongoing replication stress tolerance and clonal T cell responses distinguish liver and lung recurrence and outcomes in pancreatic cancer.

Link J, Eng J, Pelz C, MacPherson-Hawthorne K, Worth P, Sivagnanam S Nat Cancer. 2025; 6(1):123-144.

PMID: 39789181 PMC: 11779630. DOI: 10.1038/s43018-024-00881-3.

Acquired resistance to PD-L1 inhibition enhances a type I IFN-regulated secretory program in tumors.

Shi Y, McKenery A, Dolan M, Mastri M, Hill J, Dommer A EMBO Rep. 2024; 26(2):521-559.

PMID: 39663510 PMC: 11772817. DOI: 10.1038/s44319-024-00333-0.

References

Zhao C, Denison C, Huibregtse J, Gygi S, Krug R . Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways. Proc Natl Acad Sci U S A. 2005; 102(29):10200-5. PMC: 1177427. DOI: 10.1073/pnas.0504754102. View

Olivotto I, Bajdik C, Ravdin P, Speers C, Coldman A, Norris B . Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol. 2005; 23(12):2716-25. DOI: 10.1200/JCO.2005.06.178. View

Tsai M, Cook J, Chandramouli G, DeGraff W, Yan H, Zhao S . Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation. Cancer Res. 2007; 67(8):3845-52. DOI: 10.1158/0008-5472.CAN-06-4250. View

. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 365(9472):1687-717. DOI: 10.1016/S0140-6736(05)66544-0. View

Hui D, Bhasker C, Merrick W, Sen G . Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi. J Biol Chem. 2003; 278(41):39477-82. DOI: 10.1074/jbc.M305038200. View

Khodarev N, Beckett M, Labay E, Darga T, Roizman B, Weichselbaum R . STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells. Proc Natl Acad Sci U S A. 2004; 101(6):1714-9. PMC: 341831. DOI: 10.1073/pnas.0308102100. View

Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V . Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 366(9503):2087-106. DOI: 10.1016/S0140-6736(05)67887-7. View

Torres-Roca J, Eschrich S, Zhao H, Bloom G, Sung J, McCarthy S . Prediction of radiation sensitivity using a gene expression classifier. Cancer Res. 2005; 65(16):7169-76. DOI: 10.1158/0008-5472.CAN-05-0656. View

Fisher B, Anderson S, Redmond C, Wolmark N, Wickerham D, Cronin W . Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995; 333(22):1456-61. DOI: 10.1056/NEJM199511303332203. View

10.

Sotiriou C, Piccart M . Taking gene-expression profiling to the clinic: when will molecular signatures become relevant to patient care?. Nat Rev Cancer. 2007; 7(7):545-53. DOI: 10.1038/nrc2173. View

11.

Tan A, Naiman D, Xu L, Winslow R, Geman D . Simple decision rules for classifying human cancers from gene expression profiles. Bioinformatics. 2005; 21(20):3896-904. PMC: 1987374. DOI: 10.1093/bioinformatics/bti631. View

12.

van de Vijver M, He Y, Vant Veer L, Dai H, Hart A, Voskuil D . A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002; 347(25):1999-2009. DOI: 10.1056/NEJMoa021967. View

13.

Khodarev N, Minn A, Efimova E, Darga T, Labay E, Beckett M . Signal transducer and activator of transcription 1 regulates both cytotoxic and prosurvival functions in tumor cells. Cancer Res. 2007; 67(19):9214-20. DOI: 10.1158/0008-5472.CAN-07-1019. View

14.

Goldhirsch A, Glick J, Gelber R, Coates A, Thurlimann B, Senn H . Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005; 16(10):1569-83. DOI: 10.1093/annonc/mdi326. View

15.

Katz E, Kattan M . How to judge a tumor marker. Nat Clin Pract Oncol. 2005; 2(10):482-3. DOI: 10.1038/ncponc0318. View