DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node-negative breast cancer

Cancer. 2012 Feb 15;118(4):888-98. doi: 10.1002/cncr.26352. Epub 2011 Jul 14.

Abstract

Background: DEAD box 1 (DDX1) is an RNA helicase with a number of roles, including translation initiation, RNA splicing and modification, and possibly DNA double-strand break repair. Amplification of DDX1 expression has been implicated in tumors including neuroblastoma, Wilms tumor, retinoblastoma, and testicular carcinoma. The purpose of this study was to evaluate the prognostic significance of DDX1 expression in patients with breast cancer treated with breast-conserving therapy.

Methods: Paraffin-embedded specimens from 282 women with node-negative stage 1 and 2 breast cancer treated with breast-conserving surgery and radiation therapy were constructed into tissue microarrays and stained for DDX1. The molecular profiles were correlated with clinicopathologic factors and overall, local, and distant metastatic-free survival.

Results: DDX1 positivity was identified in 142 (50%) patients. The median age at diagnosis was 53 years. Eighty percent of the patients had T1 disease; 11% were HER2neu-positive, and 18% had triple-negative disease. DDX1 negativity was strongly associated with triple-negative phenotype (P = .01). DDX1 positivity was found to be associated with improved local relapse-free survival (96% vs 85%, P = .0233), distant metastatic-free survival (95% vs 85%, P = .0320), and overall survival (92% vs 84%, P = .0474) at 10 years.

Conclusions: Node-negative, early stage breast cancer patients with high levels of DDX1 were found to have a significant improvement in local control, distant metastatic-free survival, and overall survival compared with patients with low levels of DDX1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Combined Modality Therapy
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Mastectomy, Segmental
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Radiotherapy
  • Retrospective Studies
  • Sentinel Lymph Node Biopsy*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • DDX1 protein, human
  • DEAD-box RNA Helicases