Department of Chemistry, Grupo de Investigación en Química Analítica y Bioanalítica (GABIO), Universidad de los Andes, Cra. 1 No. 18ª-10, 111711, Bogotá D.C., Colombia.
Liga contra el Cáncer Seccional Bogotá, Calle 56 No. 6 - 28, 110231, Bogotá, Colombia.
J Pharm Biomed Anal. 2018 Apr 15;152:234-241. doi: 10.1016/j.jpba.2018.02.009. Epub 2018 Feb 5.
Metabolic biomarkers for breast cancer (BC) prognosis and diagnosis are required, given the increment of BC incidence rates in developing countries and its prevalence in women worldwide. Human urine represents a useful resource of metabolites for biomarker discovery, because it could reflect metabolic alterations caused by a particular pathological state. Furthermore, urine analysis is readily available, it is non-invasive and allows in-time monitoring. Therefore, in present study, a metabolic- and lipid fingerprinting of urine was performed using an analytical multiplatform approach. The study was conducted in order to identify alterated metabolites which can be helpful in the understanding of metabolic alterations driven by BC as well as their potential usage as biomarkers. Urine samples collected from healthy controls and BC subjects were analyzed using LC-MS and GC-MS. Subsequently, significantly altered metabolites were determined by employing univariate and multivariate statistical analyses. An overall decrease of intermediates of the tricarboxylic acid cycle and metabolites belonging to amino acids and nucleotides were observed, along with an increment of lipid-related compounds. Receiver operating characteristic analysis evaluated the combination of dimethylheptanoylcarnitine and succinic acid as potential urinary markers, achieving a sensitivity of 93% and a specificity of 86%. The present analytical multiplatform approach enabled a wide coverage of urine metabolites that revealed significant alterations in BC samples, demonstrating its usefulness for biomarker discovery in selected populations.
由于发展中国家乳腺癌发病率的增加以及全球范围内女性乳腺癌的流行，因此需要用于乳腺癌预后和诊断的代谢生物标志物。人类尿液是用于发现生物标志物的代谢物的有用资源，因为它可以反映特定病理状态引起的代谢变化。此外，尿液分析易于获得，非侵入性并且可以进行实时监测。因此，在本研究中，使用分析多平台方法对尿液进行了代谢和脂质指纹图谱分析。该研究旨在鉴定可能有助于理解乳腺癌驱动的代谢变化的改变代谢物及其作为生物标志物的潜在用途。使用 LC-MS 和 GC-MS 分析了来自健康对照者和乳腺癌患者的尿液样本。随后，通过使用单变量和多变量统计分析确定了明显改变的代谢物。观察到三羧酸循环中间产物和氨基酸和核苷酸代谢物的总体减少，同时脂质相关化合物增加。接收者操作特征分析评估了二甲基庚酰肉碱和琥珀酸的组合作为潜在的尿标志物，其灵敏度为 93%，特异性为 86%。该分析多平台方法能够广泛覆盖尿液代谢物，揭示了乳腺癌样本中的明显变化，证明了其在选定人群中用于生物标志物发现的有用性。
