多分析方法与多样本整合的代谢组学研究食管癌淋巴结转移生物标志物

项目名称： 多分析方法与多样本整合的代谢组学研究食管癌淋巴结转移生物标志物

项目编号： No.21505094

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张小丽

作者单位： 深圳大学

项目金额： 21万元

中文摘要： 淋巴结转移是影响食管癌预后的重要因素。目前食管癌发生淋巴结转移的机制仍不明确。发现食管癌淋巴结转移相关生物标志物对辅助临床诊断和治疗具有重要意义。本项目拟采用多分析检测方法与多样本整合的代谢组学研究思路：1）建立基于UPLC-QTOFMS和1H NMR技术的食管癌组织非靶向代谢组学分析方法。2）对食管癌淋巴结转移患者远端癌旁组织、癌组织及转移淋巴结进行非靶向代谢组学分析，筛选对淋巴结转移及预后有预警意义的差异代谢物，研究相关代谢通路。3）针对组织样本中的差异代谢物，建立基于UPLC-MS/MS技术的血清靶向代谢组学分析方法。4）对正常人、食管癌无淋巴结转移患者及食管癌淋巴结转移患者的血清进行靶向代谢组学分析，验证差异代谢物在血清中的诊断能力，进一步筛选出食管癌淋巴结转移特异性生物标志物。本研究有助于深入理解食管癌淋巴结转移的代谢机制，为食管癌临床诊断、病理分期、治疗和预后评估提供科学依据。

中文关键词： 代谢组学；生物标志物；食管癌淋巴结转移；液相色谱-质谱联用；核磁共振

英文摘要： Lymph node metastasis was an important prognostic factor for esophageal cancer. At present, the mechanism of lymph node metastasis in esophageal cancer is still not clear. The discovery of biomarkers for lymph node metastatic esophageal cancer is important for clinical diagnosis and treatment. In this project, we will use the integrated metabolomics strategy including different analytical methods and samples to look for sensitive and specific diagnostic biomarkers for esophageal cancer with lymph node metastasis. First, a ultra performance liquid chromatography combined with quadruple/time-of-flight mass spectrometry (UPLC-QTOFMS) method coupled with a proton nuclear magnetic resonance (1H NMR) spectroscopy method was developed to characterize the metabolic features of esophageal cancer. Metabolomic profiling of pairs of tissue samples and matched normal tissues including distal noncancerous tissues, tumor tissues and lymph node tumor tissues collected from lymph node metastatic esophageal cancer patients were performed by using both UPLC-QTOFMS and 1H NMR, and differential metabolites were filtered and identified from the tissue metabolome. Then，differential metabolites identified in tissues were tested in serum specimens from lymph node metastatic esophageal cancer patients, esophageal cancer patients and the healthy controls using a ultra high pressure liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) based targeted metabolomics method to confer their good diagnostic potential. This project is expected to help us to understand the metabolic mechanism of lymph node metastasis, and provide a theoretical basis for esophageal cancer clinical diagnosis, accurate staging, treatment and prognosis.

英文关键词： metabolomics;biomarkers; lymph node metastasis in esophageal cancer ; liquid chromatography-mass spectrometry ;nuclear magnetic resonance spectroscopy