口腔鳞状细胞癌病人唾液的代谢组学研究

STUDY ON SALIVA METABOLOMICS IN ORAL SQUAMOUS CELL CARCINOMA

目的选用代谢组学研究技术探求口腔鳞状细胞癌(OSCC)唾液中的风险标志物。方法采用气相色谱-飞行时间质谱(GC-TOF-MS)技术结合主成成分分析(PCA)法和正交偏最小二乘法-判别分析(OPLS-DA)法,分别对OSCC病人26例和健康人群20例唾液样本进行代谢组学研究,对比两组唾液样本的代谢轮廓,寻找两组差异代谢标志物。结果 OSCC病人和健康人群的唾液代谢轮廓存在明显差异,筛选鉴定得到6个代谢标志物:尿酸、核糖、酪氨酸、植物鞘氨醇、二氢神经鞘氨醇、对羟基乳酸。与正常人群比较,OSCC病人酪氨酸的代谢趋势上调,其余代谢物的趋势均下调。相关代谢通路分析显示,OSCC病人存在氨基酸代谢、能量代谢紊乱和脂类代谢失衡的现象,还表现出三羧酸循环异常。结论应用代谢组学研究方法可以在OSCC病人唾液中检测到代谢标志物,有助于早期预测口腔鳞癌。

Objective To investigate the risk markers of oral squamous cell carcinoma（OSCC）in saliva using metabolomics techniques. Methods Gas chromatography/time-of-flight mass spectrometry（GC-TOF-MS）,principal component analysis,and orthogonal partial least squares-discriminant analysis were performed in the saliva samples from 26 OSCC patients（OSCC group）and 20 healthy subjects（control group）.The metabolic markers of OSCC were identified by comparing the salivary metabolic profiles of the two groups. Results The GC-TOF-MS results showed that there was a significant difference in salivary metabolic profile between the two groups and six metabolic markers of OSCC were screened out and identified as uric acid,ribose,tyrosine,phytosphingosine,dihydrosphingosine,and p-hydroxyphenyllactic acid.Compared with the control group,the OSCC group had a significantly increased metabolic trend of tyrosine and decreased trends of the other metabolites.The analysis of relevant metabolic pathways showed that the OSCC patients had the disorders of amino acid metabolism and energy metabolism,the imbalance of lipid metabolism,and abnormal tricarboxylic acid cycle. Conclusion The metabolomics techniques can be used to identify the metabolic markers of OSCC in the saliva,which is helpful for the early prediction of OSCC.