Skubisz Karolina, Dąbkowski Krzysztof, Samborowska Emilia, Starzyńska Teresa, Deskur Anna, Ambrozkiewicz Filip, Karczmarski Jakub, Radkiewicz Mariusz, Kusnierz Katarzyna, Kos-Kudła Beata, Sulikowski Tadeusz, Cybula Patrycja, Paziewska Agnieszka
Institute of Health Sciences, Faculty of Medical and Health Sciences, Siedlce University of Natural Sciences and Humanities, 08-110 Siedlce, Poland.
Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Pediatric Hospital of Medical University of Warsaw, 02-091 Warsaw, Poland.
Cancers (Basel). 2023 Jun 19;15(12):3242. doi: 10.3390/cancers15123242.
Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET.
Using the AbsoluteIDQ p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography-mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients.
The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients ( < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = -1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86.
The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients' condition, helping with pharmacological treatment or dietary strategies.
胰腺癌是最常见的胰腺实体恶性肿瘤，临床病程凶险，生存率低。可靠的预后生物标志物数量有限，且需要了解胰腺肿瘤的发病机制；神经内分泌肿瘤（PNET）和胰腺导管腺癌（PDAC）促使我们分析胰腺肿瘤的血清代谢组以及PDAC和PNET代谢紊乱情况。
使用AbsoluteIDQ p180试剂盒（奥地利因斯布鲁克市的Biocrates Life Sciences AG公司）和液相色谱 - 质谱联用仪（LC - MS），我们确定了NET和PDAC患者血清中代谢物谱的变化以及代谢途径的紊乱情况。
六种代谢物的浓度在对照组和PDAC患者之间显示出统计学上的显著差异（<0.05）。与健康个体的血清样本相比，谷氨酰胺（Gln）、乙酰肉碱（C2）和瓜氨酸（Cit）在PDAC患者血清中的浓度较低，而磷脂酰胆碱aa C32:0（PC aa C32:0）、鞘磷脂C26:1（SM C26:1）和谷氨酸（Glu）的浓度较高。与PDAC相比，在PNET血清样本中，所检测的五种代谢物中的C2（FC = 8.67）和血清素（FC = 2.68）浓度较高，而磷脂酰胆碱aa C34:1（PC aa C34:1）（FC = -1.46（0.68））在PDAC样本中的浓度较高。受试者工作特征（ROC）曲线的曲线下面积（AUC）具有区分胰腺肿瘤患者的诊断能力，其中酰基肉碱的诊断能力最高：C2的AUC = 0.93，血清素的AUC = 0.85，PC aa C34:1的AUC = 0.86。
所呈现的观察结果能更好地洞察胰腺肿瘤的代谢情况，并改善肿瘤的诊断和分类。血清循环代谢物无需侵入性操作即可轻松监测，并能显示当前临床患者的状况，有助于药物治疗或饮食策略的制定。
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