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Investigating the Association of the Biogenic Amine Profile in Urine with Therapeutic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2020-08-20 , DOI: 10.1021/acs.jproteome.0c00362
Chiao Lo,Ya-Lin Hsu,Chih-Ning Cheng,Ching-Hung Lin,Han-Chun Kuo,Chiun-Sheng Huang,Ching-Hua Kuo

Neoadjuvant treatment (NAT) can downstage breast cancer and can be utilized for different clinical applications. However, the response to NAT varies among individuals. Having effective biomarkers is important to optimize the treatment of breast cancer. Concentrations of biogenic amines have been found to show an association with cancer cell proliferation, but their clinical utility remains unclear. This study developed a postcolumn-infused internal standard (PCI-IS)-assisted liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method for profiling biogenic amines in human urine. Putrescine-d8 was selected as the PCI-IS to calibrate the errors caused by matrix effects in the urine sample. The optimized method was applied to investigate the association between changes in 14 amines and the therapeutic response to NAT in breast cancer patients. Urine samples were collected before initiation of chemotherapy (n = 60). Our results indicated that the levels of N1-acetylspermine, spermidine, norepinephrine, and dopamine were significantly higher in the responder group than the nonresponder group. These metabolites were incorporated with clinical factors to identify NAT responders, and the prediction model showed an area under the curve value of 0.949. These observations provide remarkable insights for future studies in elucidating the roles of biogenic amines in breast cancer. Additionally, the PCI-IS-assisted amine profiling method can facilitate these studies.

中文翻译:

研究尿液中生物胺的分布与乳腺癌患者对新辅助化疗的治疗反应之间的关系。

新辅助治疗(NAT)可以降低乳腺癌的发病率,并可以用于不同的临床应用。但是,对NAT的响应因人而异。拥有有效的生物标志物对于优化乳腺癌的治疗很重要。已发现生物胺的浓度与癌细胞增殖有关,但其临床用途仍不清楚。这项研究开发了一种柱后注入内标(PCI-IS)辅助液相色谱与串联质谱(LC-MS / MS)相结合的方法,用于分析人尿中的生物胺。Putrescine- d 8被选作PCI-IS来校正尿样中基质效应引起的误差。该优化方法用于研究14种胺的变化与乳腺癌患者对NAT的治疗反应之间的关联。在开始化疗之前收集尿液样本(n = 60)。我们的结果表明,N 1的水平-乙酰精胺,亚精胺,去甲肾上腺素和多巴胺在无反应者组中显着高于无反应者组。将这些代谢物与临床因素结合以识别NAT应答者,预测模型显示曲线值下的面积为0.949。这些观察结果为阐明生物胺在乳腺癌中的作用为今后的研究提供了重要的见识。此外,PCI-IS辅助胺分析方法可以促进这些研究。
更新日期:2020-10-02
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