基于“半聚焦”代谢组学策略的主要消化系统肿瘤共有和特有代谢模式研究

项目名称： 基于“半聚焦”代谢组学策略的主要消化系统肿瘤共有和特有代谢模式研究

项目编号： No.31501079

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 陈天璐

作者单位： 上海交通大学

项目金额： 20万元

中文摘要： 临床样本的代谢组学研究发现，消化系统肿瘤有共同的代谢特征。全谱和靶标式代谢组学研究各有优缺点。在小样本研究的基础上，本课题拟联合采用“半聚焦”式代谢组学策略和生物信息/网络分析技术，对大规模临床样本中目标代谢物群的浓度进行精确测定，系统考察食管癌、胃癌、肝癌和大肠癌4种消化系统肿瘤的代谢关联性，筛选所有肿瘤共有和每种肿瘤特有的差异代谢物和代谢通路；借助非消化系统疾病提高其特异性；借助验证样本集对其进行优化和验证；参考临床标志物对其性能进行综合评估；最终建立消化系统肿瘤共有和特有的代谢模式。本研究将从代谢层面为消化系统肿瘤的关联研究和机制研究提供依据和线索，也为代谢调控网络的模型研究奠定实验基础。筛选出的代谢物有望成为消化系统肿瘤预防、诊断和治疗的通用和特异性靶点。建立的“半聚焦”式定量代谢组学策略可应用于其他疾病（群）特征代谢模式和代谢关联性研究。所有定量数据将通过公共数据库共享。

中文关键词： 消化系统肿瘤；代谢组学；关联分析；疾病网络；代谢模式

英文摘要： Digestive system tumors may share common metabolic defects as shown by metabolomics research on clinical samples. Both profiling and targeted metabolomic researches have their own advantages and disadvantages. After small-sample comparative study, this project will combine “semi focusing” metabolomic strategy and bioinformatics/bio-network analysis technologies to accurately measure the concentrations of dozens of target metabolites from enlarged clinical samples, to investigate the metabolic associations of 4 types of digestive system tumors (esophageal, gastric, liver and colorectal tumors) systematically, and to find out differential metabolites and pathways shared by all the tumors and specific to each type of tumors. Then, the specificity of these differential metabolites and pathways will be improved by using non-digestive system diseases. After validation and optimization by testing samples further, their diagnostic performances will be evaluated and be compared to clinical biomarkers comprehensively. Finally, the shared and specific metabolic patterns of all and each type of digestive system tumors will be established. This research may reveal metabolic evidences and clues for association and mechanism study on digestive system tumors, and meanwhile, lay the experimental foundations for metabolic regulatory network study. The key metabolites may become potential general and specific targets for the prevention, diagnosis and treatment of digestive system tumors. Our “semi focusing” quantitative metabolomic strategy could be applied to metabolic pattern and association studies on other diseases or disease groups. All the quantitative data will be uploaded to public databases.

英文关键词： digestive system tumors;metabolomics;association analysis;disease network;metabolic pattern