Understanding metabolomic characteristics of pancreatic ductal adenocarcinoma by HR-MAS NMR detection of pancreatic tissues

Abstract

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-CH2), 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.