1 Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada, Spain.
2 Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
SLAS Discov. 2017 Apr;22(4):348-359. doi: 10.1177/1087057116671490. Epub 2016 Sep 27.
Pancreatic ductal adenocarcinoma is one of the most lethal tumors since it is usually detected at an advanced stage in which surgery and/or current chemotherapy have limited efficacy. The lack of sensitive and specific markers for diagnosis leads to a dismal prognosis. The purpose of this study is to identify metabolites in serum of pancreatic ductal adenocarcinoma patients that could be used as diagnostic biomarkers of this pathology. We used liquid chromatography-high-resolution mass spectrometry for a nontargeted metabolomics approach with serum samples from 28 individuals, including 16 patients with pancreatic ductal adenocarcinoma and 12 healthy controls. Multivariate statistical analysis, which included principal component analysis and partial least squares, revealed clear separation between the patient and control groups analyzed by liquid chromatography-high-resolution mass spectrometry using a nontargeted metabolomics approach. The metabolic analysis showed significantly lower levels of phospholipids in the serum from patients with pancreatic ductal adenocarcinoma compared with serum from controls. Our results suggest that the liquid chromatography-high-resolution mass spectrometry-based metabolomics approach provides a potent and promising tool for the diagnosis of pancreatic ductal adenocarcinoma patients using the specific metabolites identified as novel biomarkers that could be used for an earlier detection and treatment of these patients.
胰腺导管腺癌是最致命的肿瘤之一，因为它通常在晚期才被发现，此时手术和/或当前的化疗疗效有限。缺乏用于诊断的敏感和特异性标志物导致预后不良。本研究的目的是鉴定胰腺导管腺癌患者血清中的代谢物，这些代谢物可用作该病理的诊断生物标志物。我们使用液相色谱-高分辨质谱进行非靶向代谢组学分析，使用来自 28 个人的血清样本，其中包括 16 名胰腺导管腺癌患者和 12 名健康对照者。多变量统计分析，包括主成分分析和偏最小二乘分析，揭示了使用非靶向代谢组学分析的液相色谱-高分辨质谱对患者和对照组的清晰分离。代谢分析显示，与对照组相比，胰腺导管腺癌患者血清中的磷脂水平明显降低。我们的结果表明，基于液相色谱-高分辨质谱的代谢组学方法为胰腺导管腺癌患者的诊断提供了一种强大而有前途的工具，使用鉴定出的特定代谢物作为新的生物标志物，可用于更早地检测和治疗这些患者。
