Metabolic Characteristics Revealing Cell Differentiation of Nasopharyngeal Carcinoma by Combining NMR Spectroscopy with Raman Spectroscopy

Background: The staging system of nasopharyngeal carcinoma (NPC) has close relationship with the degree of cell differentiation, but most NPC patients remain undiagnosed until advanced phases. Novel metabolic markers need to be characterized to support diagnose at an early stage.

Methods: Metabolic characteristics of nasopharyngeal normal cell NP69 and two types of NPC cells, including CNE1 and CNE2 associated with high and low differentiation degrees were studied by combining H NMR spectroscopy with Raman spectroscopy. Statistical methods were also utilized to determine potential characteristic metabolites for monitoring differentiation progression.

Results: Metabolic profiles of NPC cells were significantly different according to differentiation degrees. Various characteristic metabolites responsible for different differentiated NPC cells were identified, and then disordered metabolic pathways were combed according to these metabolites. We found disordered pathways mainly included amino acids metabolisms like essential amino acids metabolisms, as well as altered lipid metabolism and TCA cycle, and abnormal energy metabolism. Thus our results provide evidence about close relationship between differentiation degrees of NPC cells and the levels of intracellular metabolites. Moreover, Raman spectrum analysis also provided complementary and confirmatory information about intracellular components in single living cells. Eight pathways were verified to that in NMR analysis, including amino acids metabolisms, inositol phosphate metabolism, and purine metabolism.

Conclusions: Methodology of NMR-based metabolomics combining with Raman spectroscopy could be powerful and straightforward to reveal cell differentiation development and meanwhile lay the basis for experimental and clinical practice to monitor disease progression and therapeutic evaluation.