胰腺癌患者血清代谢组学研究

Serum metabonomic study of patients with pancreatic cancer

目的检测胰腺癌患者与健康者血清的代谢组学，筛选能够鉴别胰腺癌与健康者的差异代谢物，寻找潜在的胰腺癌早期诊断标志物。方法采用病例对照成组分析方法，以病理诊断为胰腺导管腺癌患者作为病例组，健康人群为对照组。应用高效液相色谱单级四级杆飞行时间串联质谱联用仪检测胰腺癌及健康者的血清代谢组学。通过单维及多维统计方法分析两组间代谢组学的差异，根据分子质量、代谢产物数据库和质谱／质谱（MS／MS）信息筛选差异代谢物。通过差异代谢物的受试者工作特征曲线下面积（AUC）评价它们鉴别胰腺癌及健康者的价值。结果共纳入胰腺导管腺癌患者及健康者各54例，年龄及性别相匹配。最终筛选出12种差异代谢物，其中胰腺癌患者血清中羟基花生四烯酸（HETE）、苯丙氨酸、乙酰肉碱、亚油酸、棕榈酰肉碱、亚油醇肉碱、尿嘧啶脱氧核苷酸（dUMP）和甘氨鹅脱氧胆酸8种代谢产物水平显著高于健康者；溶血磷脂酰胆碱[LysoPC（18：0）]、LysoPC（P-16：0）、溶血磷脂酸[LPA（182／0：0）]、LysoPC（14：0）4种代谢产物水平显著低于健康者（P值均〈0．05）。HETE、LysoPC（18：0）、苯丙氨酸、LPA（18：2／0：0）、dUMP的AUC分别为0．98、0．96、0．92、0．91，均大于CA19-9的AUC（0．90）。结论胰腺导管腺癌患者及健康者的血清代谢组共筛选出12种差异代谢物，其中HETE、LysoPC（18：0）、苯丙氨酸、LPA（18：2／0：0）、dUMP有可能是潜在的诊断标志物。

Objective To investigate the overall serum metabolic differences between pancreatic cancer and healthy controls and screen the different metabolites as potential diagnostic marker for early diagnosis of pancreatic cancer. Methods Case control group analysis method was used, and patients with pathological diagnosis of pancreatic ductal adenocarcinoma were considered as case group, and healthy subjects were considered as control group. UHPLC/Q-TOF MS-based metabonomics techniques were applied to analyze the difference in serum metabolites in the two groups with multivariate and univariate statistical method, and the different metabolites were screened and identified in accordance with the molecular weight, metabolites databases and MS/MS information. The diagnostic discrimination of the different metabolites was evaluated by ROC curve. Results In this study, there were 54 patients with pathological diagnosis of pancreatic ductal adenocarcinoma and 54 age and sex matched healthy controls. There were 12 kinds of different serum metabolits in the final screening and identification in the two groups. The level of hydroxy-arachidonic acid, phenylalanine, acetylcarnitine, linoleic acid, palmitoylcarnitine, linoleyl carnitine, and uracil deoxynucleotide and glycocholic chenodeoxycholic acid in serum of pancreatic cancer patients were higher than those in thecontrols （P〈0.05）. Serum LysoPC （18： 0） , LysoPC （P-16： 0） , LPA （18： 2/0： 0） , LysoPC （14： 0） in patients with pancreatic ductal adenocarcinoma were lower than those in the controls （ P 〈 0.05 ）. The AUC of HETE, LysoPC （18： 0）, phenylalanine, LPA （18： 2/0： 0）, dUMP was 0.98, 0.96, 0.92, 0.91, respectively, which were significantly higher than that of CA19-9 （0.90）. Conclusions Twelve kinds of different serum metabolits are screened and identified between pancreatic ductal adenocarcinoma patients and healthy subjects, and HETE, LysoPC （18：0）, phenylalanine, LPA （18： 2/0： 0）, dUMP may be potential markers for diagnosis of pancreatic cancer.