Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers

Hang Zhang, Xiyong Liu, Charles D. Warden, Yasheng Huang, Sofia Loera, Lijun Xue, Suzhan Zhang, Peiguo Chu, Shu Zheng, Yun Yen

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


Background: Ribonucleotide reductase (RR) is an essential enzyme involved in DNA synthesis. We hypothesized that RR subunit M2 (RRM2) might be a novel prognostic and predictive biomarker for estrogen receptor (ER)-negative breast cancers.Methods: Individual and pooled survival analyses were conducted on six independent large-scale breast cancer microarray data sets; and findings were validated on a human breast tissue set (ZJU set).Results: Gene set enrichment analysis revealed that RRM2-high breast cancers were significantly enriched for expression of gene sets that increased in proliferation, invasiveness, undifferentiation, embryonic stem/progenitor-like phenotypes, and poor patient survival (p <0.01). Independent and pooled analyses verified that increased RRM2 mRNA levels were associated with poor patient outcome in a dose-dependent manner. The prognostic power of RRM2 mRNA was comparable to multiple gene signatures, and it was superior to TNM stage. In ER-negative breast cancers, RRM2 showed more prognostic power than that in ER-positive breast cancers. Further analysis indicated that RRM2 was a more accurate prognostic biomarker for ER-negative breast cancers than the pathoclinical indicators and uPA. A new RR inhibitor, COH29, could significantly enhance the chemosensitivity to doxorubicin in ER-negative MDA-MB-231 cells, but not in ER-positive MCF-7 cells.Conclusion: RRM2 appears to be a promising prognostic biomarker and therapeutic target for ER-negative breast cancer patients.

Original languageEnglish
Article number664
JournalBMC Cancer
Issue number1
Publication statusPublished - Sept 11 2014


  • Breast cancer
  • ER-negative
  • Prognostic biomarker
  • Ribonucleotide reductase

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research


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