Structural Biochemistry Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Clin Cancer Res. 2013 Sep 1;19(17):4770-9. doi: 10.1158/1078-0432.CCR-12-2917. Epub 2013 Jul 19.
Multiple myeloma remains an incurable disease. New approaches to develop better tools for improving patient prognostication and monitoring treatment efficacy are very much needed. In this study, we aimed to evaluate the potential of metabolomics by (1)H-NMR to provide information on metabolic profiles that could be useful in the management of multiple myeloma.
Serum samples were collected from multiple myeloma patients at the time of diagnosis and after achieving complete remission. A matched control set of samples was also included in the study. The (1)H-NMR measurements used to obtain the metabolic profile for each patient were followed by the application of univariate and multivariate statistical analyses to determine significant differences.
Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids compared with the control set. A similar analysis conducted in multiple myeloma patients after achieving complete remission indicated that some of the metabolic changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a variation in the opposite direction upon responding to treatment, thus contributing to multiple myeloma patients having a closer metabolic profile to those of healthy individuals after the disappearance of major disease manifestations.
The results highlight the potential of metabolic profiles obtained by 1H-NMR in identifying multiple myeloma biomarkers that may be useful to objectively discriminate individuals with and without multiple myeloma, and monitor response to treatment.
多发性骨髓瘤仍然是一种无法治愈的疾病。非常需要新的方法来开发更好的工具,以改善患者的预后预测和监测治疗效果。在这项研究中,我们旨在通过 1 H-NMR 评估代谢组学的潜力,提供可能有助于多发性骨髓瘤治疗的代谢谱信息。
在诊断时和达到完全缓解后,从多发性骨髓瘤患者中采集血清样本。该研究还包括一组匹配的对照样本。用于获得每位患者代谢谱的 1 H-NMR 测量值随后进行单变量和多变量统计分析,以确定显著差异。
与对照组相比,多发性骨髓瘤患者在诊断时的代谢谱显示出更高水平的异亮氨酸、精氨酸、乙酸盐、苯丙氨酸和酪氨酸,以及较低水平的 3-羟基丁酸、赖氨酸、谷氨酰胺和一些脂质。在达到完全缓解的多发性骨髓瘤患者中进行的类似分析表明,在诊断时观察到的一些代谢变化(即谷氨酰胺、胆固醇、赖氨酸)在对治疗有反应时呈现出相反的变化方向,这有助于多发性骨髓瘤患者在主要疾病表现消失后,其代谢谱更接近健康个体。
研究结果强调了通过 1 H-NMR 获得的代谢谱在识别多发性骨髓瘤生物标志物方面的潜力,这些生物标志物可能有助于客观地区分有和没有多发性骨髓瘤的个体,并监测治疗反应。