Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China.
J Pharm Biomed Anal. 2020 Oct 25;190:113546. doi: 10.1016/j.jpba.2020.113546. Epub 2020 Aug 15.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal carcinomas due to an inefficient early diagnosis and a disastrous prognosis. High resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) detection of pancreatic tissues would facilitate the understanding of metabolomic characteristics of PDAC and further its clinical diagnosis by in vivo magnetic resonance spectroscopy (MRS). Pancreatic tissues from PDAC patients and Sprague-Dawley (SD) rats model and corresponding controls were detected and comparatively analyzed with HR-MAS NMR-based metabolomic strategy in order to get the underlying biomechanism and diagnostic information of PDAC. According to the univariate and multivariate statistical analysis, eight shared characteristic metabolites by PDAC patients and rats, including glycerophosphocholine (GPC), lactate, myo-inositol, methanol, taurine, methylene of lipid (L-CH), β-glucose and phosphocholine (PC), were identified as potential biomarkers of PDAC. Especially, GPC, PC and myo-inositol demonstrated high levels in pancreatic tissue and kept consistent metabolic changes both in PDAC patients and rat models. The occurrence of PDAC mainly involved the aberrations in glycerophospholipid metabolism, galactose metabolism and taurine and hypotaurine metabolism. As an in vitro alternative technique of in vivo MRS, HR-MAS NMR provided good resolution and sensitivity, thus underpinning a potential translation to the in vivo MRS setting for noninvasive detection and monitoring of clinical PDAC. The metabolic differences caused in the different species not only enhance the understanding of metabolic reprogramming of PDAC but also promote the intercommunication of PDAC metabolomes between the different species.
胰腺导管腺癌（PDAC）是最致命的癌种之一，其原因是早期诊断效率低下和预后极差。胰腺组织的高分辨率魔角旋转核磁共振（HR-MAS NMR）检测将有助于了解 PDAC 的代谢组学特征，并通过体内磁共振波谱（MRS）进一步进行临床诊断。使用基于 HR-MAS NMR 的代谢组学策略，对 PDAC 患者和 Sprague-Dawley（SD）大鼠模型以及相应对照的胰腺组织进行检测和比较分析，以获得 PDAC 的潜在生物学机制和诊断信息。根据单变量和多变量统计分析，在 PDAC 患者和大鼠中发现了 8 种具有共同特征的代谢物，包括甘油磷酸胆碱（GPC）、乳酸、肌醇、甲醇、牛磺酸、脂质亚甲基（L-CH）、β-葡萄糖和磷酸胆碱（PC），这些代谢物被认为是 PDAC 的潜在生物标志物。特别是，GPC、PC 和肌醇在胰腺组织中水平较高，在 PDAC 患者和大鼠模型中均保持一致的代谢变化。PDAC 的发生主要涉及甘油磷脂代谢、半乳糖代谢和牛磺酸和次牛磺酸代谢的异常。作为体内 MRS 的体外替代技术，HR-MAS NMR 具有良好的分辨率和灵敏度，因此为非侵入性检测和监测临床 PDAC 的体内 MRS 提供了潜在的转化。不同物种中引起的代谢差异不仅增强了对 PDAC 代谢重编程的理解，还促进了不同物种之间 PDAC 代谢组学的交流。
