Prediction of breast cancer prognosis by gene expression profile of TP53 status
Prediction of breast cancer prognosis by gene expression profile of TP53 status
复制标题
DOI：
10.1111/j.1349-7006.2007.00691.x
复制
发表时间：
2008-02-01
期刊：
影响因子：
5.7
通讯作者：
Ishioka, Chikashi
中科院分区：
文献类型：
--
作者：
Takahashi, Shin;Moriya, Takuya;Ishioka, Chikashi
TP53 突变是乳腺癌的不良预后因素。本研究旨在鉴定决定 TP53 状态表达特征（TP53 特征）的基因组，并将其与临床结果相关联。通过对 38 名日本乳腺癌患者的 TP53 基因进行全面表达分析和 DNA 测序，根据 TP53 状态，从差异表达基因中分离出一组基因。作为独立的外部数据集，引入了两个已发布的数据集，用于验证 TP53 状态预测（251 个瑞典样本）和生存分析（瑞典和 295 个荷兰样本）。通过微阵列分析鉴定出三十三个基因组。在测试集中，通过基因表达谱预测 TP53 状态的准确率为 83.3% (n = 12)。 TP53 特征能够预测 29 种 I 期和 II 期日本乳腺癌的无复发生存期 (RFS)（对数排名，P = 0.032），以及 RFS，两个独立发布的数据集的总生存期（对数排名，均 P < 0.0001）。多变量分析表明，TP53 特征是一个独立且显着的预后因素，在两个外部数据集中具有复发和生存的风险比 (HR) (P < 0.0001)。 TP53 特征在以下亚组中也是一个强有力的预后因素：雌激素受体阳性、淋巴结阳性和阴性、圣加仑标准中的中/高风险以及国家癌症研究所 (NCI) 标准中的高风险（对数等级，P < 0.0001）。 TP53 特征是手术后乳腺癌疾病结果的可靠且独立的预测因子。
TP53 mutations are a poor prognostic factor in breast cancers. The present study sets out to identify the gene set that determines the expression signature of the TP53 status (TP53 signature) and to correlate it with clinical outcome. Using comprehensive expression analysis and DNA sequencing of the TP53 gene in 38 Japanese breast cancer patients, a gene set from differentially expressed genes was isolated, depending on the TP53 status. As independent external datasets, two published datasets were introduced for validation of TP53 status predictions (251 Swedish samples) and survival analysis (both the Swedish and 295 Dutch samples). Thirty-three gene sets were identified from microarray analysis. Predictive accuracy of the TP53 status by gene expression profiling was 83.3% in the test set (n = 12). TP53 signature has the ability to predict recurrence-free survival (RFS) of 29 stage I and stage II Japanese breast cancers (log rank, P = 0.032), and RFS, overall survival of two independently published datasets (log rank, both P < 0.0001). Multivariate analysis has shown that the TP53 signature an independent and significant prognostic factor with a hazard ratio (HR) for recurrence and survival in two external datasets (P < 0.0001). The TP53 signature is also a strong prognostic factor in the subgroups: estrogen-receptor positive, lymph node positive and negative, intermediate/high risk in St. Gallen criteria, and high risk in National Cancer Institute (NCI) criteria (log rank, P < 0.0001). TP53 signature is a reliable and independent predictor of the outcome of disease in operated breast cancer.