Discovery of Potential Biomarkers with Dose- and Time-Dependence in Cisplatin-Induced Nephrotoxicity Using Metabolomics Integrated with a Principal Component-Based Area Calculation Strategy
Discovery of Potential Biomarkers with Dose- and Time-Dependence in Cisplatin-Induced Nephrotoxicity Using Metabolomics Integrated with a Principal Component-Based Area Calculation Strategy
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使用代谢组学与基于主成分的面积计算策略相结合，发现顺铂引起的肾毒性中具有剂量和时间依赖性的潜在生物标志物
DOI：
10.1021/acs.chemrestox.5b00519
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发表时间：
2016
影响因子：
4.1
通讯作者：
Xu Fengguo
中科院分区：
文献类型：
--
作者：
Zhang Pei;Chen Jiaqing;Wang Yong;Huang Yin;Tian Yuan;Zhang Zunjian;Xu Fengguo
顺铂是一种有效的化疗剂。然而，其严重的不良反应，特别是肾毒性，限制了其临床应用。为揭示顺铂肾毒性的剂量和时间依赖性，提出了基于质谱的代谢组学结合主成分面积计算（PCAC）的方法。首先构建基于主成分分析模型前两个主成分的面积图。然后，计算PC-T曲线下累积面积之和（AUCPC-T）。最后，计算不同时间点实验组和对照组之间AUCPC-T的倍数变化，并用作指示性参数。与PCAC的方法，顺铂诱导的代谢变化的剂量和时间依赖性首次得到定量证实。筛选出27个与顺铂肾毒性相关的具有剂量和时间依赖性的潜在生物标志物。顺铂阻断的代谢途径主要包括能量代谢、氨基酸代谢和脂质代谢。
Cisplatin is a potent chemotherapeutic agent. However, its clinical usage is restricted by serious adverse effects, especially nephrotoxicity. For revealing the dose- and time-dependence of cisplatin-induced nephrotoxicity, mass spectrometry-based metabolomics integrated with a principal component-based area calculation (PCAC) strategy was proposed in the present study. Area plots based on the first two principal components of the principal component analysis model were constructed first. Then, the sums of cumulative areas under PC-T curves (AUCPC-T) were calculated. Finally, the fold change of AUCPC-Tbetween experimental and control groups at different time points was calculated and used as an indicative parameter. With the PCAC approach, dose- and time-dependence of cisplatin-induced metabolic change was quantitatively confirmed for the first time. Furthermore, 27 potential biomarkers with dose- and time-dependence related to nephrotoxicity induced by cisplatin were screened out and tentatively identified. Metabolic pathways interrupted by cisplatin mainly included energy, amino acid, and lipid metabolism.