整合代谢组学与质谱分子成像及检测技术的食管癌快速筛查及早期诊断新方法研究

项目名称： 整合代谢组学与质谱分子成像及检测技术的食管癌快速筛查及早期诊断新方法研究

项目编号： No.21335007

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 再帕尔阿不力孜

作者单位： 中国医学科学院药物研究所

项目金额： 300万元

中文摘要： 本项目围绕食管癌发生发展与内源性代谢物变化的相关性等关键科学问题，采用代谢组学方法与质谱新技术相结合的分析思路，开展寻找与食管癌发生发展及其诊断相关生物标志物的快速筛查及原位分析新方法研究。本项目拟从临床样本、动物模型与细胞模型三个层次，首先采用组合式离子化方式的LC-MS/MS非靶向代谢组学与针对低含量代谢物的代谢轮廓分析方法，获取全面的代谢物信息，寻找食管癌相关的可能生物标志物。进一步考察可能标志物在癌症发展不同阶段的变化规律，并结合新型常压敞开式离子化质谱与分子成像新技术（AFAI-MS与AFAI-IMS），对相关标志物进行快速检测、原位分析及分布特征研究，获得与食管癌发生发展及其诊断相关的潜在生物标志物（群），并进行生物学功能验证。通过基于AFAI-MS和LC-MS/MS的标志物靶向定量方法及定量指标，建立以小分子生物标志物（群）为主要指标进行食管癌快速筛查及早期诊断的新分析手段。

中文关键词： 食管癌;代谢组学;常压敞开式离子化质谱;LC-MS/MS;生物标志物

英文摘要： This project focuses on the significant correlations between the occurrence, progression of esophageal cancer and the changes of endogenous metabolites. Combining metabolomics and novel homemade ambient mass spectrometry technique, a new approach for rapid screening and in situ analysis of biomarkers relevant to esophageal cancer could be established. The project will take clinical samples, animal models and cell models as the research objects. Firstly, non-targeted metabolomics analysis using integrated ionization LC-MS/MS approach will be performed to acquire the information of global metabolites and metabolic profiling will aim at the low abundance metabolites with significant bioinformation, and the obtained results will be used to discover potential biomarkers of esophageal cancer. The variation features and distribution characterization of potential biomarkers will be further investigated, through rapid detection and in situ analysis by using novel homemade ambient mass spectrometry (AFAI-MS) and molecular imaging (AFAI-IMS) technique, and the potential biomarkers will be verified by elucidation of biological function relevant to the occurrence, progression and diagnosis of esophageal cancer. In a word, we aim to establish a novel approach of rapid screening and early diagnosis of esophageal cancer by indexing and monitoring the small molecular biomarkers based on AFAI-MS and LC-MS/MS targeted quantitative methods.

英文关键词： esophageal cancer;metabolomics;ambient mass spectrometry ;LC-MS/MS;biomarkers