PO.MCB09.02 · 分子与细胞生物学
黑人非洲裔胰腺导管腺癌患者中代谢与炎症之间的关联
The link between metabolism and inflammation in Black African pancreatic ductal adenocarcinoma patients
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：胰腺导管腺癌（PDAC）仍是全球最致死的癌症之一，在黑人非洲裔人群中的发病率不断上升。新出现的证据表明，代谢失调与炎症之间的相互作用可能在PDAC的发病和进展中起关键作用。然而，这一关系在非洲队列中仍未得到充分研究。
方法：我们使用核磁共振（NMR）波谱对来自知情同意参与者的血浆样本进行了非靶向代谢组学研究，参与者包括81例PDAC患者（57例可切除、15例局部晚期、9例转移性）、6例慢性胰腺炎患者和6例健康对照。活性氧（ROS）水平使用OxiSelect™体外ROS/RNS检测试剂盒（绿色荧光）定量。组间比较采用Wilcoxon和Kruskal-Wallis秩和检验，相关性和生存评估分别采用Spearman相关分析和Kaplan-Meier分析。p值 < 0.05被认为具有统计学意义。
结果：总胆红素（p = 0.004）、结合胆红素（p = 0.003）、丙氨酸氨基转移酶（p = 0.01）和天冬氨酸氨基转移酶（p = 0.03）水平在各组间显著改变。代谢组学分析显示，随着肿瘤分期进展，2-羟基丁酸（2-HB，p = 0.004）和乙酰乙酸（p = 0.009）水平升高。PDAC患者被分层为2-HB“高”组和“正常/低”组，其中最高的25%代表“高”组。此外，较低的2-HB浓度与更长的生存结局相关。尽管无统计学意义，2-HB高的患者与2-HB低的患者相比表现出ROS/RNS水平升高。2-HB与炎症标志物之间存在正相关：GlycA（rho=0.07，p=0.64）、GlycB（rho=0.07，p=0.66）、CRP（rho=0.49，p=0.08）和白细胞计数（rho=0.48，p=0.08）。
结论：本研究证明了黑人非洲裔PDAC患者中代谢通路改变与氧化应激之间的潜在关联。升高的2-HB和乙酰乙酸可能作为肿瘤进展和预后不良的代谢指标。这些发现凸显了整合代谢和炎症分析以更好地理解非洲人群PDAC生物学的重要性。
查看英文原文 English abstract
Background: Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most lethal cancers globally, with increasing incidence among Black African populations. Emerging evidence suggests that the interplay between metabolic dysregulation and inflammation may play crucial roles in the pathogenesis and progression of PDAC. However, this relationship remains underexplored in African cohorts.
Methods: We conducted an untargeted metabolomics study using Nuclear Magnetic Resonance (NMR) spectroscopy on plasma samples obtained from consenting participants comprising 81 PDAC patients (57 resectable, 15 locally advanced, and 9 metastatic), 6 chronic pancreatitis patients, and 6 healthy controls. Reactive oxygen species (ROS) levels were quantified using the OxiSelect™ In Vitro ROS/RNS Assay Kit (Green Fluorescence). Group comparisons were performed using Wilcoxon and Kruskal-Wallis rank-sum tests, while Spearman's correlation and Kaplan-Meier analyses were applied for correlation and survival assessment. A p-value < 0.05 was considered statistically significant.
Results: Total bilirubin ( p = 0.004), conjugated bilirubin ( p = 0.003), alanine aminotransferases ( p = 0.01) and aspartate aminotransferases ( p = 0.03) levels were significantly altered across the groups. Metabolomic profiling revealed elevated levels of 2-hydroxybutyrate (2-HB, p = 0.004) and acetoacetate ( p = 0.009) with advancing tumor stage. PDAC patients were stratified into “high” and “normal/low” 2-HB groups, with the top 25% representing the “high” group. Furthermore, lower 2-HB concentrations were associated with longer survival outcomes. Although not statistically significant, patients with high 2-HB exhibited increased ROS/RNS levels compared to those with low 2-HB. There was a positive correlation between 2-HB and inflammatory markers: GlycA (rho=0.07, p =0.64), GlycB (rho=0.07, p =0.66), CRP (rho=0.49, p =0.08) and White cell count (rho=0.48, p =0.08).
Conclusion: This study demonstrates a potential link between altered metabolic pathways and oxidative stress in Black African PDAC patients. Elevated 2-HB and acetoacetate may serve as metabolic indicators of tumor progression and poor prognosis. These findings highlight the importance of integrating metabolic and inflammatory profiling to better understand PDAC biology in African populations.
利益披露 Disclosure
N. Elebo, None..
D. Ojo, None..
J. A. Omoshoro-Jones, None..
S. Cacciatore, None..
J. Devar, None..
E. E. Nweke, None.