| 摘要: |
| 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。 |
| 关键词: 胆管肿瘤 肝外胆管癌 代谢组学 气相色谱-质谱法 主成分分析 |
| DOI：10.3724/SP.J.1008.2015.00383 |
| 投稿时间：2015-01-27修订日期：2015-03-19 |
| 基金项目:上海市科委西医引导类创新基金(124119a1101),新一轮上海市卫生系统优秀青年人才培养计划(XYQ2011030),上海市优秀学科带头人计划(13XD1400200). |
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| Peri-operative bile metabonomics changes of extrahepatic cholangiocarcinoma and prognosis analysis |
| CUI Long-jiu1,LI Zhi-shuai2,TAN Wei-feng2*,JIANG Xiao-qing2* |
(1. Department of Special Treatment Ⅱ, Eastern Hepatobliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China;
2. Department of Biliary Tract Surgery Ⅰ, Eastern Hepatobliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
*Corresponding authors) |
| Abstract: |
| Objective To screen for molecular markers associated with the prognosis of extrahepatic cholangiocarcinoma (EHCC) after radical excision by observing the difference of bile metabolomics during perioperative period. Methods Twenty-seven patients with EHCC, including 19 with hilar cholangiocarcinoma and 8 with distal cholangiocarcinoma, were included in this study. Their bile samples were collected before and 1, 7 days after operation. Metabonomics method using gas chromatography-mass spectrometry(GC-MS)was employed to analyze the different metabolites at different time points. Correlation analysis was performed between the common different metabolites and the patient prognosis. Results Five kinds of metabolites in the bile were notably increased 1 day after operation compared with that before operation, no metabolites were decreased. Three kinds of metabolites were notably increased and another 3 were notably decreased 7 days after operation compared with before operation. Among the above two groups of different metabolites, there were 2 common metabolites: benzoic acid and methylmalonic acid. The one year recurrence rate of patients with benzoic acid increased ≥2 times at 7 days after operation was significantly lower than that increased <2 times (P=0.04). No significant correlation was found between the change of methylmalonic acid and the early relapse in 1 year after operation. Moreover, bivariate correlation showed that the changes of benzoic acid metaboilic level in bile were not significantly correlated with the serum CA19-9, age of patients, or TNM stage (P>0.05). Conclusion The change of benzoic acid metaboilic level in bile during perioperative period can help to predict the early relapse in extrahepatic cholangiocarcinoma patients after curative resection. |
| Key words: bile duct neoplasms extrahepatic cholangiocarcinoma metabolomics gas chromatography-mass spectrometry principal component analysis |
