中国地鼠口腔颊囊鳞癌组织的非靶代谢组学分析  

Non-target metabolomic analysis of buccal pouch squamous cell carcinoma in Chinese hamsters

作　　者：张锐虎 王渊 续国强 高继萍 宋国华 陈朝阳 轩瑞晶 ZHANG Ruihu;WANG Yuan;XU Guoqiang;GAO Jiping;SONG Guohua;CHEN Zhaoyang;XUAN Ruijing(Laboratory Animal Center of Shanxi Medical University,Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Models,China,030001 Taiyuan;Department of Microbiology and Immunology,School of Basic Medicine,Shanxi Medical University,Taiyuan)

机构地区：[1]实验动物与人类疾病动物模型山西省重点实验室,山西医科大学实验动物中心,太原030001 [2]山西医科大学基础医学院微生物与免疫学教研室

出　　处：《实用口腔医学杂志》2024年第5期608-613,共6页Journal of Practical Stomatology

基　　金：国家自然科学基金面上项目(编号:31970513);中央引导地方科技发展项目(编号:YDZJSX2022A060);山西省教育厅高校科技创新项目(编号:2020L0185);山西省青年科学基金项目(编号:20210302124414);山西省专利转化专项计划项目(编号:202202047);实验动物新资源创制与利用山西省科技创新人才团队项目(编号:202204051002032)。

摘　　要：目的:探讨口腔鳞状细胞癌(OSCC)发病的代谢基础及相关分子机制。方法:将20只中国地鼠分为模型组和对照组(n=10),采用化学诱导法建立颊囊黏膜鳞癌模型;色谱-质谱联用鉴定2组鼠颊囊的代谢物,以正交偏最小二乘判别分析模型的变量权重值>1和P<0.05为标准,筛选两组样本中的差异代谢物,进行KEGG通路富集分析。结果:二甲基苯并蒽-石蜡油溶液涂抹18周,模型组地鼠颊囊有弥漫性白斑分布、乳头状突起明显,病理学诊断为高分化鳞癌;脂类和类脂质分子是癌变组织和正常组织的主要差异代谢物;不饱和脂肪酸生物合成重编程、胆固醇积累、色氨酸分解代谢增强、天冬氨酸上调、嘧啶和嘌呤合成增加等是OSCC发生发展中的重要代谢特征。结论:靶向相关代谢途径的分子干预,有望抑制OSCC发病和进展。Objective:To explore the metabolic basis and related molecular mechanism of oral squamous cell carcinoma(OSCC)pathogenesis.Methods:20 Chinese hamsters were divided into 2 groups(n=10).OSCC models were induced by dimethylbenzanthracene(DMBA)in 10 of the animals and the other 10 were used as the controls.LC-MS chromatography-mass spectrometry was used to identify the metabolites in the buccal pouch,and multidimensional statistical analysis of the metabolites was performed with the orthogonal partial least squares discriminant analysis model.Variable Importance for the Projection(VIP)>1 and P<0.05 were used as the criteria to screen the differential metabolites between the 2 groups.KEGG pathway annotation and enrichment analysis for the metabolites were performed to screen the significantly differential pathways.Results:The hamster cheek pouches painted with 0.5%DMBA for 18 weeks were diffused with leukoplakia and loaded obvious papillary protrusions,which were diagnosed as OSCC by pathological examination.Lipids and lipid-like molecules were the main differential metabolites.Reprogramming of unsaturated fatty acid biosynthesis,cholesterol accumulation,enhanced catabolism of tryptophan,up-regulation of aspartate,increased synthesis of pyrimidine and purine,etc.were important metabolic features in the occurrence and development of OSCC.Conclusion:Molecular intervention targeting the related metabolic pathways is expected to inhibit OSCC pathogenesis and progression.

关 键 词：中国地鼠 口腔颊囊鳞癌 组织非靶代谢组 

分 类 号：R739.8[医药卫生—肿瘤]