鼻咽癌诊断和治疗的新标志物(英文)

Novel potential markers of nasopharyngeal carcinoma for diagnosis and therapy

目的采用代谢组学技术寻找鼻咽癌诊断和治疗的标志物。方法采用气-质联用(GS-MS)技术,检测了49例鼻咽癌患者(Ⅰ期19例,Ⅱ期17例,Ⅲ期13例),37例喉癌患者和40个健康人血清中52种内源性代谢物。结果代谢谱比较分析结果显示,犬氨酸、N-乙酰葡萄酰胺、硬脂酸、甘氨酸、N-乙酰半乳糖胺、N-乙酰葡萄胺和对羟基丙酮酸在鼻咽癌患者血清中显著升高(～3倍)(P<0.05),其中犬氨酸、N-乙酰葡萄酰胺、N-乙酰半乳糖胺、N-乙酰葡萄胺和对羟基丙酮酸在鼻咽癌Ⅰ到Ⅲ逐步升高(P<0.05),治疗后该5种内源性代谢物逐步降低,且恢复到正常水平(P<0.05)。其中4种代谢物犬氨酸、N-乙酰葡萄酰胺、N-乙酰葡萄胺和对羟基丙酮酸水平降低与鼻咽癌治疗后肿瘤减小率成正相关,因此其可作为鼻咽癌潜在标志物。此外,这4个代谢物还与鼻咽癌复发转移有关。结论犬氨酸、N-乙酰葡萄酰胺、N-乙酰葡萄胺和对羟基丙酮酸是鼻咽癌变和侵袭重要的代谢产物。

【Objective】To search for biomarkers of nasopharyngeal carcinoma（NPC） for early diagnosis and therapy.【Methods】51 serum metabolites were evaluated from 49 patients with NPC（19 stage Ⅰ,17 stage Ⅱ,13 stage Ⅲ）,37 patients with throat cancer and 40 healthy controls,using a combination of high-throughput gas chromatography and mass spectrometry.【Results】Compared metabolic profiling revealed that kynurenine,N-acetylglucosaminylamine,stearic acid,glycine,N-acetylgalactosamine,N-acetylglucosamine and hydroxyphenylpyruvate were highly increased（～3-fold） in NPC patient sera（P 0.05）.Further,the concentration of five metabolites including kynurenine,N-acetylglucosaminylamine,N-acetylglucosamine,N-acetylgalacto-samine and hydroxyphenylpyruvate gradually increased from stage Ⅰ to stage Ⅲ（P 0.05）.After radiotherapy,these five endogenous metabolites decreased gradually,and tended to approach a normal level（P 0.05）.Four metabolites—Kynurenine,N-acetylglucosaminylamine,N-acetylglucosamine and Hydroxyphenylpyruvate were positively associated with rate of tumor reduction,and thus they may serve as potential markers of NPC.These same four metabolites were also highly increased with NPC recurrence and/or metastasis.【Conclusions】Kynurenine,N-acetylglucosaminylamine,N-acetylglucosamine,N-acetylgalactosamine and hydroxyphenyl pyruvate are potentially important metabolic intermediaries of cancer cell invasiveness and aggressivity.