期刊
BMC CANCER
卷 14, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2407-14-664
关键词
Ribonucleotide reductase; Breast cancer; ER-negative; Prognostic biomarker
类别
资金
- Major State Basic Research Development Program of China, 973 Program [2004CB518707]
- Zhejiang Provincial Natural Science Foundation of China [R2090353]
- US National Institutes of Health [R01 CA127541]
- China Scholarship Council
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据