Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers.
Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers.
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DOI：
10.1186/1471-2407-14-664
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发表时间：
2014-09-11
期刊：
影响因子：
3.8
通讯作者：
Yen Y
中科院分区：
文献类型：
--
作者：
Zhang H;Liu X;Warden CD;Huang Y;Loera S;Xue L;Zhang S;Chu P;Zheng S;Yen Y
核糖核苷酸还原酶 (RR) 是参与 DNA 合成的必需酶。我们假设 RR 亚基 M2 (RRM2) 可能是雌激素受体 (ER) 阴性乳腺癌的一种新型预后和预测生物标志物。对六个独立的大规模乳腺癌微阵列数据集进行了个体和汇总生存分析；并在人类乳腺组织组（ZJU 组）上验证了研究结果。基因集富集分析显示，RRM2 高乳腺癌的基因集表达显着富集，这些基因集的增殖、侵袭性、未分化、胚胎干/祖细胞样表型和患者生存率较差 (p<0.01)。独立和汇总分析证实，RRM2 mRNA 水平升高与患者预后不良相关，且呈剂量依赖性。 RRM2 mRNA 的预后能力与多基因特征相当，并且优于 TNM 分期。在 ER 阴性乳腺癌中，RRM2 比 ER 阳性乳腺癌显示出更强的预后能力。进一步分析表明，RRM2 是比病理临床指标和 uPA 更准确的 ER 阴性乳腺癌预后生物标志物。一种新的 RR 抑制剂 COH29 可以显着增强 ER 阴性 MDA-MB-231 细胞对阿霉素的化疗敏感性，但不能增强 ER 阳性 MCF-7 细胞对阿霉素的化疗敏感性。 RRM2 似乎是 ER 阴性乳腺癌患者的一个有前途的预后生物标志物和治疗靶点。本文的在线版本 (doi:10.1186/1471-2407-14-664) 包含补充材料，可供授权用户使用。
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. 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). 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. RRM2 appears to be a promising prognostic biomarker and therapeutic target for ER-negative breast cancer patients. The online version of this article (doi:10.1186/1471-2407-14-664) contains supplementary material, which is available to authorized users.
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核糖核苷酸还原酶小亚基M2B预测结直肠癌的生存更好。
影响因子：
11.2
作者：
Liu X;Lai L;Wang X;Xue L;Leora S;Wu J;Hu S;Zhang K;Kuo ML;Zhou L;Zhang H;Wang Y;Wang Y;Zhou B;Nelson RA;Zheng S;Zhang S;Chu P;Yen Y
通讯作者：
Yen Y
影响因子：
9.8
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
通讯作者：
Brown PO
DOI：
10.1186/bcr3402
发表时间：
2013-03-14
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Habel LA;Sakoda LC;Achacoso N;Ma XJ;Erlander MG;Sgroi DC;Fehrenbacher L;Greenberg D;Quesenberry CP Jr
通讯作者：
Quesenberry CP Jr
影响因子：
168.9
作者：
Huang, E;Cheng, SH;Huang, AT
通讯作者：
Huang, AT
影响因子：
8.8
作者：
Millar, E. K. A.;Graham, P. H.;McNeil, C. M.;Browne, L.;O'Toole, S. A.;Boulghourjian, A.;Kearsley, J. H.;Papadatos, G.;Delaney, G.;Fox, C.;Nasser, E.;Capp, A.;Sutherland, R. L.
通讯作者：
Sutherland, R. L.