Abstract:
Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS)-an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for a more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (Nuclear Magnetic Resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic profiles of the MGUS patients revealed lower levels of alanine, lysine, leucine but higher levels of formic acid when compared to controls. However, metabolic profiling of MM patients, compared to controls, exhibited decreased levels of total Apolipoprotein-A1, HDL-4 Apolipoprotein-A1, HDL-4 Apolipoprotein-A2, HDL Free Cholesterol, HDL-3 Cholesterol and HDL-4 Cholesterol. Lastly, metabolic comparison between MGUS to MM patients primarily indicated alterations in lipoproteins levels: Total Cholesterol, HDL Cholesterol, HDL Free Cholesterol, Total Apolipoprotein-A1, HDL Apolipoprotein-A1, HDL-4 Apolipoprotein-A1 and HDL-4 Phospholipids. This study provides novel insights into the serum metabolic and lipoprotein subfraction changes in patients as they progress from a healthy state to MGUS to MM, which may allow for earlier clinical detection and treatment.
摘要:
多发性骨髓瘤(MM)是一种无法治愈的血液肿瘤。在此之前是意义不确定的单克隆丙种球蛋白病(MGUS)-无症状期。已证明早期检测可提高5年生存率。然而,缺乏能够早期检测疾病的血液生物标志物.代谢组学和脂蛋白亚组分变量分析正在获得牵引力,以扩大我们对疾病状态的理解,更具体地说,用于鉴定血液肿瘤患者的诊断标志物。本研究旨在增强我们对多发性骨髓瘤(MM)的理解,并确定候选代谢物,允许更有效的预防性治疗。从25名健康对照中收集血清,20名MGUS患者,和30名MM患者。利用1H-NMR(核磁共振)波谱来评估血清样品。使用多变量检查代谢物浓度,单变量,和路径分析。MGUS患者的代谢谱显示丙氨酸水平较低,赖氨酸,与对照组相比,亮氨酸但甲酸含量较高。然而,MM患者的代谢谱,与对照组相比,表现出降低的总载脂蛋白A1,HDL-4载脂蛋白A1,HDL-4载脂蛋白A2,HDL游离胆固醇,HDL-3胆固醇和HDL-4胆固醇。最后,MGUS与MM患者之间的代谢比较主要表明脂蛋白水平的改变:总胆固醇,HDL胆固醇,HDL游离胆固醇,总载脂蛋白-A1、HDL载脂蛋白-A1、HDL-4载脂蛋白-A1和HDL-4磷脂。这项研究为患者从健康状态到MGUS再到MM的血清代谢和脂蛋白亚组分变化提供了新的见解。这可能允许早期临床检测和治疗。