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目的根据围手术期胆汁代谢组学差异,筛选出与肝外胆管癌根治性切除术后相关的胆汁分子标志物。方法选择27例肝外胆管癌患者(19例肝门部胆管癌,8例远端胆管癌),分别收集其外科切除术前、切除术后第1和第7天的胆汁。采用基于气相色谱-质谱联用(GC-MS)的代谢组学方法,分别对比分析术后第1天与术前、术后第7天与术前胆汁中的差异代谢物,并对共同的差异代谢物与患者预后进行相关性分析。结果术后第1天与术前相比,胆汁内有5种代谢物升高,无代谢物降低;术后第7天与术前相比,胆汁内有3种代谢物升高,3种代谢物降低。以上两组差异代谢物中,有2种相同物质:苯甲酸和甲基丙二酸。术后第7天与术前比较苯甲酸升高≥2倍的患者1年内复发率低于升高<2倍的患者(P=0.04),而手术前后甲基丙二酸的变化与术后1年内早期复发无相关性。通过对苯甲酸在术后第7天较术前变化倍数与CA19-9分级、术前年龄分级、术后TNM病理分期进行双变量相关性分析,提示均无明显相关性(P>0.05)。结论围手术期胆汁内苯甲酸代谢水平的变化程度有助于预测肝外胆管癌患者根治性切除术后早期复发。
Objective To select the bile molecular markers associated with radical resection of extrahepatic cholangiocarcinoma based on perioperative bile metabolomics. Methods Twenty-seven patients with extrahepatic cholangiocarcinoma (19 cases of hilar cholangiocarcinoma and 8 cases of distal cholangiocarcinoma) were selected and their bile were collected before surgery and 1 and 7 days after the resection. Metabolomic methods based on gas chromatography-mass spectrometry (GC-MS) were used to compare and analyze the difference metabolites in the bile between the first day of operation and the seventh day after operation and preoperatively, respectively, Correlation analysis of different metabolites and prognosis of patients. Results On the first day after operation, there were 5 metabolites in the bile increased compared with the preoperative ones without any decrease of metabolites. On the 7th day after operation, compared with the preoperative, there were 3 metabolites within the bile and 3 Metabolites decrease. Among the above two groups of difference metabolites, there are two kinds of the same substances: benzoic acid and methylmalonic acid. Patients on the 7th day after surgery had a> 1-fold higher recurrence rate than patients with elevated <2-fold higher benzoic acid (P = 0.04) than those preoperatively (P = 0.04) 1 year early relapse no correlation. The bivariate correlation analysis of benzoic acid on the 7th day after operation compared with preoperative CA19-9, preoperative age grade and postoperative TNM pathological stage showed no significant correlation (P> 0.05). Conclusions Perioperative changes in the level of bile benzoic acid metabolism are helpful to predict the early recurrence of patients with extrahepatic cholangiocarcinoma after radical resection.