Metabolic profiling of a cohort of pancreatic ductal adenocarcinoma (PDAC) patients of african ancestry

Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is deadly cancer with dysregulated metabolism being one of its key features, affecting several processes such as immune response. Studying metabolism in PDAC especially in under-studied population groups could lead to the identification of biomarkers and in better understanding of the immune response. We aimed to identify dysregulated metabolites in PDAC progression and their possible role in the immune response. Method: Blood samples were collected from 34 PDAC, 6 CP, and 6 healthy volunteers, all of African ancestry (M190681). Nuclear Magnetic Resonance (NMR) spectroscopy and Reactive Oxygen Species (ROS) analyses were used to identify metabolites and quantify ROS, respectively. The R studio V1.3 was used for statistical analysis and a p-value of <0.05 was considered significant. Results: Preliminary results from the study showed that tyrosine (p-value:0.001), histidine (p-value:0.004), acetate (p-value:0.002) and 3-hydroxybutyrate (p-value:0.018) levels were elevated as the disease progressed. Total Bilirubin exceeded the normal threshold of 5-21 μmol/L for the PDAC patients. Mortality occurred earlier for patients with inorganic phosphates (p-value: 0.229) higher than 1.42 mmol/L and anion gap (p-value: 0.002) higher than the threshold 9-16 mmol/L. Furthermore, patients having C-reactive protein (CRP) < 200mg/L and metabolic value of GlycA < 1.1 survived longer than 150 days. ROS was elevated in resectable (p-value:0.003) and Locally advanced (p-value:0.008) PDAC when compared with HC. Conclusion: Dysregulated metabolism is associated with increased ROS which has been shown to be linked to immunosuppression. The combination of dysregulated metabolites, ROS, and clinical parameters may have potential utility in disease stratification, management, and future therapeutic targeting.