Bodnarczuk Tomasz, Deskur Anna, Dolegowska Katarzyna, Dolegowska Barbara, Starzynska Teresa, Blogowski Wojciech
Department of Gastroenterology, Pomeranian Medical University Szczecin, Poland.
Department of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University Szczecin, Poland.
Am J Cancer Res. 2018 Sep 1;8(9):1865-1872. eCollection 2018.
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.
先前的实验报告表明，花生四烯酸（AA）的脂氧合酶（LOX）衍生物，如羟基二十碳四烯酸（HETEs），可能在胰腺癌的发病机制中具有重要意义。然而，这些观察结果尚未在临床研究中得到证实。在本研究中，我们全面评估了胰腺腺癌患者（n = 36）、慢性胰腺炎患者（n = 39）和健康个体（n = 35）中选定的LOX衍生HETEs（如5-、12-和15-HETE）的全身水平。与健康个体相比，胰腺腺癌患者的5-、12-和15-HETE水平高出3至8倍（至少P<0.003）。在慢性胰腺炎患者中也观察到了类似的结果，与健康志愿者相比，所有检测的HETE酸浓度均升高（在所有情况下至少P<0.03）。有趣的是，在我们的患者中，检测的HETEs水平与胰腺癌的TNM分期没有显著相关性。最后，受试者工作特征曲线分析表明，所有检测的HETEs在区分胰腺腺癌与非癌性疾病方面的曲线下面积值相对较低（0.49 - 0.61；每种情况下P>0.05）。我们的研究为所检测的HETEs在人类胰腺癌和其他胰腺疾病的临床发病机制中的重要性提供了首个初步临床证据。此外，我们的数据表明，此处检测的HETEs没有显示出足够的临床潜力，不能用作区分人类胰腺腺癌与其他非癌性疾病的独立（生物）标志物。
