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

研究成果: 雜誌貢獻文章

19 引文 (Scopus)

摘要

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.
原文英語
文章編號664
期刊BMC Cancer
14
發行號1
DOIs
出版狀態已發佈 - 九月 11 2014
對外發佈Yes

指紋

Estrogen Receptors
Estrogens
Breast Neoplasms
Ribonucleotide Reductases
Biomarkers
Therapeutics
Messenger RNA
MCF-7 Cells
Survival Analysis
ribonucleotide reductase M2
Doxorubicin
Genes
Breast
Phenotype
Gene Expression
Survival
DNA
Enzymes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics
  • Medicine(all)

引用此文

Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers. / Zhang, Hang; Liu, Xiyong; Warden, Charles D.; Huang, Yasheng; Loera, Sofia; Xue, Lijun; Zhang, Suzhan; Chu, Peiguo; Zheng, Shu; Yen, Yun.

於: BMC Cancer, 卷 14, 編號 1, 664, 11.09.2014.

研究成果: 雜誌貢獻文章

Zhang, H, Liu, X, Warden, CD, Huang, Y, Loera, S, Xue, L, Zhang, S, Chu, P, Zheng, S & Yen, Y 2014, 'Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers', BMC Cancer, 卷 14, 編號 1, 664. https://doi.org/10.1186/1471-2407-14-664
Zhang, Hang ; Liu, Xiyong ; Warden, Charles D. ; Huang, Yasheng ; Loera, Sofia ; Xue, Lijun ; Zhang, Suzhan ; Chu, Peiguo ; Zheng, Shu ; Yen, Yun. / Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers. 於: BMC Cancer. 2014 ; 卷 14, 編號 1.
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abstract = "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.",
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T1 - Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers

AU - Zhang, Hang

AU - Liu, Xiyong

AU - Warden, Charles D.

AU - Huang, Yasheng

AU - Loera, Sofia

AU - Xue, Lijun

AU - Zhang, Suzhan

AU - Chu, Peiguo

AU - Zheng, Shu

AU - Yen, Yun

PY - 2014/9/11

Y1 - 2014/9/11

N2 - 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.

AB - 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.

KW - Breast cancer

KW - ER-negative

KW - Prognostic biomarker

KW - Ribonucleotide reductase

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