Pharmacometabolomics study identifies circulating spermidine and tryptophan as potential biomarkers associated with the complete pathological response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer.
Pharmacometabolomics study identifies circulating spermidine and tryptophan as potential biomarkers associated with the complete pathological response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer.
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DOI：
10.18632/oncotarget.9489
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发表时间：
2016-06-28
期刊：
影响因子：
--
通讯作者：
Corona G
中科院分区：
文献类型：
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作者：
Miolo G;Muraro E;Caruso D;Crivellari D;Ash A;Scalone S;Lombardi D;Rizzolio F;Giordano A;Corona G
确定预测治疗效果和不良事件的生物标志物是指导患者选择个性化癌症治疗的关键任务。在本研究中，我们应用药物代谢组学方法来鉴定HER-2阳性乳腺癌患者对曲妥珠单抗-紫杉醇新辅助治疗的病理完全缓解可能相关的生物标志物。根据组织学反应，34例患者被分为两组：良好反应组（n = 15）和不良反应组（n = 19）。采用液相色谱-串联质谱法分析所有患者治疗前血清靶向代谢组学谱，采用多变量偏最小二乘法判别分析两组患者代谢组学谱的差异。区分两组患者最相关的代谢物是亚精胺和色氨酸。与不良应答者相比，良好应答者亚精胺水平较高，色氨酸水平较低（p < 0.001, q < 0.05）。这两种代谢物的血清水平鉴别达到病理完全缓解的患者，敏感性为90%[0.79-1.00]，特异性为0.87%[0.67-1.00]。这些初步结果支持个体患者的代谢在决定癌症治疗反应中所起的作用，并可能成为选择更有可能从曲妥珠单抗-紫杉醇治疗中获益的患者的有用工具。
Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. In the present study, we applied a pharmacometabolomics approach to identify biomarkers potentially associated with pathological complete response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer patients. Based on histological response the 34 patients enrolled in the study were subdivided into two groups: good responders (n = 15) and poor responders (n = 19). The pre-treatment serum targeted metabolomics profile of all patients were analyzed by liquid chromatography tandem mass spectrometry and the differences in the metabolomics profile between the two groups was investigated by multivariate partial least squares discrimination analysis. The most relevant metabolites that differentiate the two groups of patients were spermidine and tryptophan. The Good responders showed higher levels of spermidine and lower amounts of tryptophan compared with the poor responders (p < 0.001, q < 0.05). The serum level of these two metabolites identified patients who achieved a pathological complete response with a sensitivity of 90% [0.79–1.00] and a specificity of 0.87% [0.67–1.00]. These preliminary results support the role played by the individual patients' metabolism in determining the response to cancer treatments and may be a useful tool to select patients that are more likely to benefit from the trastuzumab-paclitaxel treatment.