摘要
目的:运用组织代谢组学方法,探讨肝细胞肝癌的发病机制与治疗策略。方法:采用GC-MS分析肝细胞肝癌(Hepatocellular Carcinoma,HCC)患者癌组织和癌旁组织中的内源性小分子代谢产物,进行单维和多维统计分析,寻找差异代谢物。通过KEGG和HMDB数据库检索和分析,获得相关代谢通路。结果:经PCA、PLS-DA分析得知癌组织和癌旁组织的代谢轮廓具有显著性差异,经OPLS-Loading plot分析寻找到25个差异性代谢产物,与之相关代谢通路有36条,多属于糖代谢、氨基酸代谢和线粒体转移代谢。25个差异物中ROC曲线下面积大于0.8的差异物有16个,经分析该16个差异物与三磷酸腺苷结合盒(ATP-binding Cassette,ABC)转运体代谢、半乳糖代谢、氨基糖和核苷酸代谢有关。结论:肝癌组织细胞中存在沃伯格效应(Warburg effect),即糖酵解异常增强,三羧酸循环减弱。线粒体转运功能异常、钴含量的升高,均可能与Warburg effect相关。能量代谢异常是肝癌的发病机制之一,阻断相关代谢通路有望成为靶向治疗的新途径。
The present study aimed to research pathogenesis and therapeutics of hepatocellular carcinoma （HCC） with the method of tissue metabolomics. A combined gas chromatography - mass spectrometry. （GC - MS） method was developed suitable for analyzing the endogenous small molecule of liver cancer tissues and adjacent tissues. The unidimensional and multidimensional statistics were used to look for differential metabolites. And then, the KEGG and HMDB database were utilized to find related differential pathways and pathogenesis of HCC. The PCA and PLS-DA showed that there were significant differences on the endogenous small molecule of liver cancer tissues and adjacent tissues. Through the OPLS-Loading plot analysis, there were 25 differential metabolites and 36 relevant pathways. The differential pathways belong to carbohydrate metabolism, amino acid metabolism and mitochondrial transfer. There were 16 metabolites＇ area under the ROC curve which was bigger than 0.8, which were related with ATP-binding cassette （ABC） transporters, galactose metabolism, amino sugar and nueleotide sugar metabolism. It was concluded that the Warburg effect exists in HCC cells. The energy of HCC cell was from glycolytic function, because the glycolysis was enhanced and the citric acid cycle decreased. Mitochondrial dysfunction and the increased cobalt content may correlate with the Warburg effect, which may be one of the pathogenesis of liver cancer, and expected to become the breakthrough point of a new targeting therapeutic approach.
作者
李君
孙淑军
王洋
刘才峰
仲兴阳
徐峰
蔡志刚
张永煜
Li Jun Sun Shujun Wang Yang Liu Caifeng Zhong Xingyang Xu Feng Cai Zhigang Zhang Yongyu(Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China School of Traditional Dai Medicine, West Yunnan University of Applied Sciences, Xishuangbanna 600100, China Unimicro （Shanghai） Technologies Co. Ltd., Shanghai 201203, China Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)
出处
《世界科学技术-中医药现代化》
CSCD
2017年第4期578-586,共9页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金面上项目(81373519):基于整体代谢网络的异病同证(三焦)湿热证的证候基础及病变机制研究
负责人:张永煜
上海市科委项目(13401900306):黄芩总黄酮苷元有效组分抗肾纤维化的成药性研究
负责人:张永煜
关键词
肝细胞肝癌
肿瘤组织
代谢组学
沃伯格效应
Hepatocellular carcinoma, tumor tissue, metabonomics, Warburg effect
