Abstract
BackgroundThe 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.MethodsMetabolic 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 1H NMR spectroscopy with Raman spectroscopy. Statistical methods were also utilized to determine potential characteristic metabolites for monitoring differentiation progression.ResultsMetabolic 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.ConclusionsMethodology 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.
Highlights
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
Metabolic profiles of nasopharyngeal carcinoma cells differed from differentiation High quality of 1H nuclear magnetic resonance (NMR) spectra from cell and media samples (Additional file 1: Figure S1), including control media are acquired
In the 1H NMR spectra, aliphatic regions are dominated by various metabolites, containing numerous resonances from amino acids like essential amino acids (EAAs, including isoleucine, leucine, valine, lysine), non-essential amino acids, tricarboxylic acid (TCA) intermediates, and others metabolites
Summary
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. Nasopharyngeal carcinoma (NPC) is a non-lymphomatous, squamous cell carcinoma that arises from epithelial cells on the surface of nasopharynx It is a common head and neck cancer in South China and Southeast Asia, where the annual incidence ranges from 20 to 50 per 100,000 people [1]. Current diagnostic method is based on clinical history, endoscopic examination, and a biopsy of the lesion [5], as well as a series of radiological tests [6] These examinations are difficult for early diagnosis of NPC, and invasive for patients. To improve the overall prognosis and reduce mortality rate of NPC patients, it is critical for researchers to develop effective strategies from cellular level for monitoring differentiation progression and therapeutic evaluation
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