Chen Yang, Chen Zhong, Su Ying, Lin Donghong, Chen Min, Feng Shangyuan, Zou Changyan
1Department of Laboratory Medicine, Fujian Medical University, Fuzhou, 350004 China.
2Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 China.
Cancer Cell Int. 2019 Feb 18;19:37. doi: 10.1186/s12935-019-0759-4. eCollection 2019.
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.
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.
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.
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.
鼻咽癌（NPC）的分期系统与细胞分化程度密切相关，但大多数鼻咽癌患者直到晚期才被诊断出来。需要鉴定新的代谢标志物以支持早期诊断。
通过将核磁共振氢谱（1H NMR）与拉曼光谱相结合，研究鼻咽正常细胞NP69以及两种不同分化程度的鼻咽癌细胞（包括高分化的CNE1和低分化的CNE2）的代谢特征。还利用统计方法确定用于监测分化进程的潜在特征性代谢物。
根据分化程度，鼻咽癌细胞的代谢谱有显著差异。鉴定出了负责不同分化程度鼻咽癌细胞的各种特征性代谢物，然后根据这些代谢物梳理了紊乱的代谢途径。我们发现紊乱的途径主要包括必需氨基酸代谢等氨基酸代谢，以及脂质代谢、三羧酸循环的改变和能量代谢异常。因此，我们的结果提供了证据，证明鼻咽癌细胞的分化程度与细胞内代谢物水平之间存在密切关系。此外，拉曼光谱分析还提供了关于单个活细胞内成分的补充和验证信息。有八条途径在核磁共振分析中得到了验证，包括氨基酸代谢、磷酸肌醇代谢和嘌呤代谢。
基于核磁共振的代谢组学方法与拉曼光谱相结合，能够强有力且直接地揭示细胞分化发展，同时为监测疾病进展和治疗评估的实验及临床实践奠定基础。
