Lipoxins and Resolvins in Patients With Pancreatic Cancer: A Preliminary Report

Abstract

Eicosanoids are bioactive lipids derived from arachidonic acid, which have emerged as key regulators of a wide variety of pathophysiological processes in recent times and are implicated as mediators of gastrointestinal cancer. In this study, we investigated the systemic levels of lipoxygenase (LOX)-derived lipoxin A4 and B4, together with resolvin D1 and D2 in patients with pancreatic adenocarcinoma (n = 68), as well as in healthy individuals (n = 32). Systemic concentrations of the aforementioned immunoresolvents were measured using an enzyme-linked immunosorbent assay (ELISA). In this study, we observed that compared with concentrations in healthy individuals, the peripheral concentrations of the aforementioned eicosanoids were significantly elevated (2- to 10-fold) in patients with pancreatic cancer (in all cases p<0.00001). No significant association was observed between eicosanoid levels and the TNM clinical staging. Furthermore, we observed no significant differences in concentrations of the analyzed bioactive lipids between patients diagnosed with early-stage (TNM stage I-II) and more advanced disease (TNM stage III-IV). Receiver operating characteristic (ROC) curve analysis of each aforementioned immunoresolvent showed area under the curve values ranging between 0.79 and 1.00. Sensitivity, specificity, as well as positive and negative predictive values of the eicosanoids involved in the detection/differentiation of pancreatic adenocarcinoma ranged between 56.8% and 100%. In summary, our research is the first study that provides clinical evidence to support a systemic imbalance in LOX-derived lipoxins and resolvins as the mechanism underlying the pathogenesis of pancreatic adenocarcinoma. This phenomenon occurs regardless of the clinical TNM stage of the disease. Furthermore, our study is the first to preliminarily highlight the role of peripheral levels of immunoresolvents, particularly resolvin D1, as potential novel biomarkers of pancreatic cancer in humans.