Metabolic responses to the occurrence and chemotherapy of pancreatic cancer: biomarker identification and prognosis prediction

Abstract

AbstractAs the most malignant tumor, the prognosis of pancreatic cancer is not ideal even in the small number of patients who can undergo radical surgery. As a highly heterogeneous tumor, chemotherapy resistance is a major factor leading to decreased efficacy and postoperative recurrence of pancreatic cancer. In this study, nuclear magnetic resonance (NMR)-based metabolomics was applied to identify serum metabolic characteristics of pancreatic ductal adenocarcinoma (PDAC) and screen the potential biomarkers for its diagnosis. Metabolic changes of patients with different CA19-9 levels during postoperative chemotherapy were also monitored and compared to identify the differential metabolites that may affect the efficacy of chemotherapy. Finally, 19 potential serum biomarkers were screened to serve the diagnosis of PDAC, and significant metabolic differences between the two CA19-9 stratifications of PDAC were involved in energy metabolism, lipid metabolism, amino acid metabolism, and citric acid metabolism. Enrichment analysis of metabolic pathways revealed six shared pathways by PDAC and chemotherapy such as alanine, aspartate and glutamate metabolism, arginine biosynthesis, glutamine and glutamate metabolism, citrate cycle, pyruvate metabolism, and glycogolysis/gluconeogeneis. The similarity between the metabolic characteristics of PDAC and the metabolic responses to chemotherapy provided a reference for clinical prediction of benefits of postoperative chemotherapy in PDAC patients.