Schmitt Esther, Végran Frédérique, Chevrier Sandy, Burillier Laura, Cadouot Muriel, Lizard-Nacol Sarab, Coudert Bruno, Fumoleau Pierre, Arnould Laurent, Boidot Romain
Molecular Biology Unit, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France.
Platform for Transfer to Cancer Biology, Centre Georges-François Leclerc, 1, rue du Professeur Marion, Dijon, 21079 Cedex, France.
BMC Cancer. 2015 Mar 24;15:169. doi: 10.1186/s12885-015-1198-9.
Overexpression of HER2 is observed in 20 to 30% of breast carcinomas. The use of trastuzumab has improved the treatment of these patients, especially when it is associated with docetaxel. To optimize the use of this treatment, it seems important to select putative complete responders before treatment administration.
In this study, we analyzed by quantitative PCR the expression of 28 genes in HER2-overexpressing tumors treated with trastuzumab + docetaxel-based chemotherapy. We then correlated their expression profile with those of trastuzumab-sensitive and resistant cell lines to classify tumors as having a sensitive (pCR) or resistant (non-pCR) profile. Finally, we used public datasets from the GEO website to validate the reduced gene-expression profile obtained.
We identified an 8-gene-expression combination that predicted the response to treatment with an accuracy of 76%. Based on public microarray data, we showed that the expression profile was specific to first-line trastuzumab + docetaxel-based treatment with an accuracy of 85%.
Our results showed that by profiling the expression of 8 genes it was possible to predict the response to first-line trastuzumab + docetaxel-based chemotherapy. The use of cancer cell lines as the reference allowed a proper fit with the specificity of different tissues, such as lung or gastric cancers, which could also be eligible to concomitant HER2 inhibition by treatment with trastuzumab or tyrosine kinase inhibitors and docetaxel.
20%至30%的乳腺癌中观察到HER2过表达。曲妥珠单抗的使用改善了这些患者的治疗，尤其是与多西他赛联合使用时。为了优化这种治疗的使用，在给予治疗前选择可能的完全缓解者似乎很重要。
在本研究中，我们通过定量PCR分析了接受基于曲妥珠单抗+多西他赛化疗的HER2过表达肿瘤中28个基因的表达。然后我们将它们的表达谱与曲妥珠单抗敏感和耐药细胞系的表达谱相关联，以将肿瘤分类为具有敏感（pCR）或耐药（非pCR）谱。最后，我们使用来自GEO网站的公共数据集来验证获得的简化基因表达谱。
我们确定了一种8基因表达组合，其预测治疗反应的准确率为76%。基于公共微阵列数据，我们表明该表达谱对于基于曲妥珠单抗+多西他赛的一线治疗具有特异性，准确率为85%。
我们的结果表明，通过分析8个基因的表达，可以预测对基于曲妥珠单抗+多西他赛的一线化疗的反应。使用癌细胞系作为参考能够与不同组织（如肺癌或胃癌）的特异性良好匹配，这些组织也可能适合通过曲妥珠单抗或酪氨酸激酶抑制剂与多西他赛联合治疗来同时抑制HER2。
