Introduction: 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. Methods: Plasma samples were collected from fasted individuals with resectable PDAC (n= 23, median age 68 [IQR 56–75], 69.6% male) and HV (n= 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. Results: 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). Discussion: In conclusion, using metabolomics, biochemical differences between resectable PDAC and HV were detected. These differences indicate metabolic plasticity and utilization of alternative fuel sources.
引言：胰腺导管腺癌（PDAC）起病隐匿，由于肿瘤进展过晚侵犯局部结构或已发生远处转移，确诊患者中仅15-20%适合手术切除。其特有的肿瘤微环境不仅形成保护屏障限制化疗药物疗效，同时阻碍PDAC细胞所需营养物质的输送。为应对此困境，肿瘤细胞通过代谢适应寻求替代能量来源。本研究旨在探索可切除PDAC患者与健康志愿者（HV）之间的代谢组学差异，具体目标是通过核磁共振（NMR）波谱与质谱（MS）技术，验证可切除PDAC是否引发足以区分两组人群的代谢适应与变异。方法：采集空腹状态下可切除PDAC患者（n=23，中位年龄68岁[IQR 56-75]，男性占69.6%）与HV（n=24，中位年龄63岁[IQR 58-71]，男性占54.2%）的血浆样本，于南安普顿大学医院采用NMR及Biocrates MxP Quant 500试剂盒进行分析。结果：NMR波谱鉴定出6种能显著区分PDAC与HV组的独立代谢物，包括血浆浓度升高的3-羟基丁酸与柠檬酸，以及浓度降低的谷氨酰胺与组氨酸。MS分析发现84种代谢物在两组间存在显著差异，其中PDAC群体中变化倍数（FC）>1.5的代谢物为结合型胆汁酸（牛磺胆酸、甘氨胆酸及甘氨鹅脱氧胆酸）。讨论：本研究通过代谢组学技术成功检测到可切除PDAC与HV之间的生化差异，这些差异揭示了肿瘤细胞的代谢可塑性及替代能源利用机制。
Metabolite Changes Associated with Resectable Pancreatic Ductal Adenocarcinoma
肿瘤(癌症)患者之家