McDonnell Declan, Afolabi Paul R, Niazi Umar, Wilding Sam, Griffiths Gareth O, Swann Jonathan R, Byrne Christopher D, Hamady Zaed Z
Human Development & Health, University of Southampton, Southampton SO16 6YD, UK.
Department of General Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK.
Cancers (Basel). 2025 Mar 29;17(7):1150. doi: 10.3390/cancers17071150.
Pancreatic ductal adenocarcinoma (PDAC) is insidious, with only 15-20% of those diagnosed suitable for surgical resection as it is either too advanced and has invaded local structures or has already spread to distant sites. The associated tumor microenvironment provides a protective shield which limits the efficacy of chemotherapeutic agents, but also impairs the delivery of nutrients required for the PDAC cells. To compensate for this, metabolic adaptions occur to provide alternative sources of fuel. The aim of this study is to explore metabolomic differences between participants with resectable PDAC compared to healthy volunteers (HV). The objectives were to use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to determine if resectable PDAC induces sufficient metabolic adaptations and variations which could be used to discriminate between the two groups.
Plasma samples were collected from fasted individuals with resectable PDAC ( = 23, median age 68 [IQR 56-75], 69.6% male) and HV ( = 24, median age 63 [IQR 58-71], 54.2% male). Samples were analyzed using NMR and the Biocrates MxP Quant 500 kit at University Hospital Southampton.
NMR spectroscopy identified six independent metabolites that significantly discriminated between the PDAC and HV groups, including elevated plasma concentrations of 3-hydroxybutyrate and citrate, with decreased amounts of glutamine and histidine. MS analysis identified 84 metabolites with a significant difference between the PDAC and HV cohorts. The metabolites with a fold change (FC) > 1.5 in the PDAC population were conjugated bile acids (taurocholic acid, glycocholic acid, and glycochenodexoycholic acid).
In conclusion, using metabolomics, biochemical differences between resectable PDAC and HV were detected. These differences indicate metabolic plasticity and utilization of alternative fuel sources.
胰腺导管腺癌（PDAC）隐匿性强，确诊患者中仅15 - 20%适合手术切除，因为要么病情已进展至侵犯局部结构，要么已扩散至远处部位。相关的肿瘤微环境形成了一个保护屏障，这不仅限制了化疗药物的疗效，还损害了PDAC细胞所需营养物质的供应。为了弥补这一点，会发生代谢适应以提供替代燃料来源。本研究的目的是探索可切除PDAC患者与健康志愿者（HV）之间的代谢组学差异。目标是使用核磁共振（NMR）光谱和质谱（MS）来确定可切除PDAC是否会引发足够的代谢适应和变化，从而用于区分这两组人群。
从禁食的可切除PDAC患者（n = 23，中位年龄68岁[四分位间距56 - 75岁]，69.6%为男性）和HV（n = 24，中位年龄63岁[四分位间距58 - 71岁]，54.2%为男性）采集血浆样本。样本在南安普敦大学医院使用NMR和Biocrates MxP Quant 500试剂盒进行分析。
NMR光谱鉴定出六种独立的代谢物，可显著区分PDAC组和HV组，包括血浆中3 - 羟基丁酸和柠檬酸盐浓度升高，而谷氨酰胺和组氨酸含量降低。MS分析鉴定出84种在PDAC组和HV队列之间存在显著差异的代谢物。在PDAC人群中变化倍数（FC）> 1.5的代谢物是结合胆汁酸（牛磺胆酸、甘氨胆酸和甘氨鹅脱氧胆酸）。
总之，通过代谢组学检测到了可切除PDAC与HV之间的生化差异。这些差异表明了代谢可塑性以及替代燃料来源的利用情况。
