title: DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer.
abstract: Breast cancer is a heterogeneous disease characterized by diverse molecular signatures and a variable response to therapy. Clinical management of breast cancer is guided by the expression of estrogen and progesterone receptors and HER2 amplification. New prognostic and predictive markers, as well as additional targets for therapy, are needed for more effective management of this disease. Gene expression microarrays were probed with RNAs from 176 primary breast cancer samples and tissue microarrays immunostained with anti-DDX1 antibody, an antibody to DEAD box protein DDX1, a putative RNA-RNA and RNA-DNA unwinding protein normally found in the nucleus. Half of the patient cohort had experienced early relapse despite standard adjuvant therapy, but were otherwise matched for estrogen receptor and HER2 status, stage and duration of follow-up. Here, we identify DDX1 RNA overexpression as an independent prognostic marker for early recurrence in primary breast cancer, with a hazard ratio of 4.31 based on logrank analysis of Kaplan-Meier curves. Elevated levels of DDX1 protein in the cytoplasm also independently correlate with early recurrence with a hazard ratio of 1.90. In conclusion, our data indicate a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1. We propose that elevated levels of DDX1 RNA or the presence of DDX1 in the cytoplasm could serve as an effective prognostic biomarker for early recurrence in primary breast cancer.
authors.affiliation: Department of Oncology, School of Cancer/Engineering/Imaging Sciences, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada.
authors.forename: Devon R
authors.initials: DR
authors.lastname: Germain
authors.forename: Kathryn
authors.initials: K
authors.lastname: Graham
authors.forename: Darryl D
authors.initials: DD
authors.lastname: Glubrecht
authors.forename: Judith C
authors.initials: JC
authors.lastname: Hugh
authors.forename: John R
authors.initials: JR
authors.lastname: Mackey
authors.forename: Roseline
authors.initials: R
authors.lastname: Godbout
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D021381:Protein Transport; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C086252:DDX1 protein, human; D053487:DEAD-box RNA Helicases