A population-based gene signature is predictive of breast cancer survival and chemoresponse.
A population-based gene signature is predictive of breast cancer survival and chemoresponse.
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DOI：
10.3892/ijo_00000536
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发表时间：
2010-03
影响因子：
5.2
通讯作者：
Guo NL
中科院分区：
文献类型：
--
作者：
Rathnagiriswaran S;Wan YW;Abraham J;Castranova V;Qian Y;Guo NL
提高复发或转移性乳腺癌患者的生存率仍然是一个关键问题。这项研究试图在广泛的患者人群中，包括那些患有晚期疾病的患者中，基于28个基因签名开发一种预后方案。获得了1，734名乳腺癌患者的临床注释转录谱，以验证28个基因标记在预后分类中的作用。在Kaplan-Meier分析中，28个基因签名产生了关于乳腺癌无病生存期（对数秩P < 0.0001; n = 1，337）和总生存期（对数秩P < 0.0001; n = 806）的显著患者分层。基因表达特征提供了每个经典临床病理因素定义的亚组中无病生存期的精确预后（对数秩P < 0.006; Kaplan-Meier分析），包括LN-、LN+、ER-、ER+和肿瘤II级。此外，研究了这种基因特征是否预测了对通常用于治疗乳腺癌的药物的化学反应。NCI-60细胞系中该基因标记的mRNA表达水平用于预测对CMF、他莫昔芬、紫杉醇、多西他赛和阿霉素（阿霉素）的化学反应。28个基因的预后标记准确地预测了对所研究的药物的化疗反应（P < 0.02）。这项研究证实了乳腺癌基因标签在广泛的临床环境中的预后适用性。这种预后特征也可预测癌细胞系中的药物反应。
It remains a critical issue to improve the survival rate in patients with recurrent or metastatic breast cancer. This study sought to develop a prognostic scheme based on a 28-gene signature in a broad patient population, including those with advanced disease. Clinically annotated transcriptional profiles of 1,734 breast cancer patients were obtained to validate the 28-gene signature in prognostic categorization. The 28-gene signature generated significant patient stratification with regard to breast cancer disease-free survival (log-rank P < 0.0001; n = 1,337) and overall survival (log-rank P < 0.0001; n = 806) in Kaplan-Meier analyses. The gene expression signature provides refined prognosis of disease-free survival (log-rank P < 0.006; Kaplan-Meier analysis) within each classic clinicopathologic factor-defined subgroup, including LN-, LN+, ER-, ER+, and tumor Grade II. Furthermore, it was investigated whether this gene signature predicts chemoresponse to drugs commonly used to treat breast cancer. The mRNA expression levels of this gene signature in NCI-60 cell lines were used to predict chemoresponse to CMF, Tamoxifen, Paclitaxel, Docetaxel, and Doxorubicin (Adriamycin). The 28-gene prognostic signature accurately (P < 0.02) predicted chemotherapeutic response to the studied drugs. This study confirmed the prognostic applicability of the breast cancer gene signature in a broad clinical setting. This prognostic signature is also predictive of drug response in cancer cell lines.
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DOI：
10.1016/j.engappai.2006.01.004
发表时间：
2006-06-01
影响因子：
8
作者：
Eick, Christoph F.;Rouhana, Alain;Vilalta, R.
通讯作者：
Vilalta, R.
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D
DOI：
10.1007/978-3-642-01805-3_5
发表时间：
2009-01-01
期刊：
SIMILARITY-BASED CLUSTERING: RECENT DEVELOPMENTS AND BIOMEDICAL APPLICATIONS
影响因子：
--
作者：
Strickert, Marc;Schleif, Frank-Michael;Seiffert, Udo
通讯作者：
Seiffert, Udo
影响因子：
3.8
作者：
McShane, Lisa M.;Altman, Douglas G.;Clark, Gary M.
通讯作者：
Clark, Gary M.
影响因子：
168.9
作者：
Huang, E;Cheng, SH;Huang, AT
通讯作者：
Huang, AT