Unidad de Investigación, Instituto de Investigación Sanitaria IdIPAZ, Hospital Universitario La Paz, Paseo de la Castellana 261, Madrid 28046, Spain.
BMC Cancer. 2010 Jun 28;10:336. doi: 10.1186/1471-2407-10-336.
Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.
We included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.
An 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.
This study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.
基因表达谱分析可能会提高早期乳腺癌患者的预后准确性。我们的目的是证明开发一种简单的分子特征来预测远处复发是可行的。
我们纳入了 153 例激素受体阳性的 I 期和 II 期乳腺癌患者。从福尔马林固定石蜡包埋样本中分离 RNA,并使用基因表达检测进行 83 个基因的 qRT-PCR 扩增。我们分析的基因包括 70 基因签名、复发评分和双基因指数中的基因。使用 Cox 回归模型分析基因表达与临床变量和远处无复发生存之间的关联。
定义了一个 8 个基因的预后评分。根据预后评分定义的低危患者 5 年远处无复发生存率为 97%,而高危患者为 60%。多变量分析中,8 基因评分仍然是一个显著的因素,其性能与两个经过验证的基因谱相似:70 基因签名和复发评分。该特征的有效性在从 GEO 数据库获得的独立队列中得到了验证。
本研究确定了一种简单的基因表达评分,可补充乳腺癌的组织病理学预后因素,并可在石蜡包埋样本中确定。