A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer
A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer
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DOI：
10.1038/nm.1908
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发表时间：
2009-01-01
期刊：
影响因子：
82.9
通讯作者：
Delorenzi, Mauro
中科院分区：
文献类型：
--
作者：
Farmer, Pierre;Bonnefoi, Herve;Delorenzi, Mauro
为了更好地了解肿瘤-宿主相互作用与化疗疗效之间的关系，我们开发了一种分析方法来量化基因表达数据集中观察到的几种生物学过程。我们对接受化疗的雌激素受体阴性乳腺癌患者的肿瘤活检进行了测试。我们报告了EORTC 10994/BIG 00-01试验中基质基因表达增加预测了受试者对术前5-氟尿嘧啶、表阿霉素和环磷酰胺（FEC）化疗的耐药性。基质标记的预测值在接受化疗但未接受治疗的对照组的两个独立受试者队列中成功验证，表明标记是预测性的而不是预后性的。根据对显微切割乳腺肿瘤样本数据的重新分析，特征中的基因在反应性间质中表达。这些发现确定了一种以前未描述的FEC治疗耐药机制，并表明抗基质药物可能提供克服化疗耐药的新方法。
To better understand the relationship between tumor-host interactions and the efficacy of chemotherapy, we have developed an analytical approach to quantify several biological processes observed in gene expression data sets. We tested the approach on tumor biopsies from individuals with estrogen receptor-negative breast cancer treated with chemotherapy. We report that increased stromal gene expression predicts resistance to preoperative chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in subjects in the EORTC 10994/BIG 00-01 trial. The predictive value of the stromal signature was successfully validated in two independent cohorts of subjects who received chemotherapy but not in an untreated control group, indicating that the signature is predictive rather than prognostic. The genes in the signature are expressed in reactive stroma, according to reanalysis of data from microdissected breast tumor samples. These findings identify a previously undescribed resistance mechanism to FEC treatment and suggest that antistromal agents may offer new ways to overcome resistance to chemotherapy.