A Preliminary Study On Plasma Lipid Histology Of Nasopharyngeal Carcinoma Based On UPLC - MS Technique

Objective:Nasopharyngeal carcinoma (NPC) is a malignance which originates in the epithelium of nasopharynx. It is characterized by high recurrence rate and early distant metastasis. The staging is directly related to prognosis. However, due to the non-specific symptoms, the difficulty of clinical examination and lacking an effective and simple detective method, most patients are diagnosed only when the tumor has reached an advanced stage. It is reported that Epstein-Barr virus can affect lipid metabolism of the hosted cells. Since Epstein-Barr virus is closely associated with the occurrence of NPC and can be detected in the premalignant lesions of nasopharyngeal epithelium, lipidomics research in NPC is worth doing. The lipidomics study of the NPC may contribute to searching early diagnostic biomarkers and understanding the mechanism of oncogenesis. Our study focused on finding potential biomarkers and alterations in the metabolic pathway by analyzing the lipidomics difference between the patients and the healthy controls.Methods:A lipidomics strategy based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was applied to analyze the plasma samples from 10 healthy controls and 10 newly-diagnosed NPC patients before treatment.Results:In the UPLC-MS data of all samples,6914 variables were acquired in positive ion mode and 4004 variables were acquired in negative ion mode. The original data matrix was well-clustered observed by principle component analysis and established groupings with respect to NPC patients and healthy controls by partial least squares-discrimination analysis.500-fold cross validation was employed to select the optimal number of variables and evaluate the predictive ability of orthogonal projections to latent structures discriminant analysis model. The loading plots, score plots and variable importance on projection were compared and the disturbance of noise and isotopes was eliminated to select candidate metabolites. By searching the 136 candidate metabolites in the database,29 of them can be found their chemical formulas. In our study, metabolites belong to fatty acids, glycerolipids, glycerophospholipids and saccharolipids were higher in the NPC patients, while ceramide belonging to sphingolipids was lower.Conlusion:Abnormal levels of lipid metabolites indicated that lipid metabolism was disturbed in NPC and potential biomarkers can be found by further investigation. The biological significance of the selected metabolites was discussed and possible changes in the metabolic pathways were proposed in this study.