Previous experimental reports have demonstrated that lipoxygenase (LOX) derivatives of arachidonic acid (AA), such as hydroxyeicosatetraenoic acids (HETEs), may be of significance in the pathogenesis of pancreatic cancer. However, these observations have not been confirmed in clinical studies. In the current study, we comprehensively evaluated the systemic levels of selected LOX-derived HETEs such as 5-, 12- and 15-HETE in patients with pancreatic adenocarcinoma (n=36), chronic pancreatitis (n=39), and in healthy individuals (n=35). Compared to healthy individuals, patients with pancreatic adenocarcinoma showed 3-8-fold higher levels of 5-, 12- and 15-HETE (at least P<0.003). Similar results were observed in patients with chronic pancreatitis, who had elevated concentrations of all examined HETE acids compared to healthy volunteers (in all cases at least P<0.03). Interestingly, the levels of the examined HETEs were not significantly associated with the TNM stage of pancreatic cancer in our patients. Finally, analyses of receiver operating characteristic curves demonstrated that all HETEs examined had relatively low area under the curve values for discriminating pancreatic adenocarcinoma from non-cancerous conditions (0.49-0.61; P>0.05 in each case). Our study provides first preliminary clinical evidence for the significance of the examined HETEs in the clinical pathogenesis of pancreatic cancer and other pancreatic diseases in humans. Moreover, our data demonstrate that the HETEs examined here do not show sufficient clinical potential to be used as independent (bio)markers for differentiating pancreatic adenocarcinoma from other non-cancerous conditions in humans.
Keywords: Arachidonic acid; hydroxyeicosatetraenoic acids; lipoxygenase; pancreatic cancer.