Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry.

Nnenna Elebo,Geoffrey Candy,Jones Omoshoro-Jones,John Devar,Ekene Emmanuel Nweke,Pascaline N Fru,Martin Smith,Christiaan De Wet Van Zyl,Stefano Cacciatore,Luiz F Zerbini,Barend Christiaan Vorster

doi:10.3390/metabo11100663

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.

Highlights

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most fatal cancers, primarily due to its late-stage presentation and resistance to therapy [1]
The demographic features were matched across the four patient groups (i.e., chronic pancreatitis (CP), Resectable Pancreatic Adenocarcinoma (RPC), LAPC and MPC)
Five of the PDAC patients developed cholangitis, an inflammation of the bile duct system often caused by bacterial infection, and this was higher in patients with more advanced stages of PDAC

Summary

Introduction

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most fatal cancers, primarily due to its late-stage presentation and resistance to therapy [1]. Over 80% of PDAC patients are diagnosed with locally advanced or metastatic disease and, cannot undergo surgery [3]. Classic symptoms of PDAC include weight loss, anorexia, abdominal pain, and obstructive jaundice [6]. Some of the risk factors of PDAC include age, obesity, smoking, excessive alcohol intake, chronic pancreatitis (CP), and Type 2 Diabetes Mellitus (T2DM) [7]. There is very little biological information on PDAC in the African population, they have been shown to have increased incidence and mortality, attributed to a combination of social (such as excessive smoking and alcohol intake) and genetic factors [8,9,10]

Methods

Results

Conclusion