The link between metabolism and inflammation in Black African pancreatic ductal adenocarcinoma patients

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.