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血清和尿液代谢组学分析揭示了与鼻咽癌相关的代谢途径和生物标志物。

Serum and urine metabolomics analyses reveal metabolic pathways and biomarkers in relation to nasopharyngeal carcinoma.

作者信息

Liao Zhaohui, Zhao Li, Zhong Fangyan, Zhou Yumeng, Lu Tianzhu, Liu Lijuan, Gong Xiaochang, Li Jingao, Rao Jun

机构信息

Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, People's Republic of China.

School of Nursing, Nanchang University, Nanchang, Jiangxi, China.

出版信息

Rapid Commun Mass Spectrom. 2023 Mar 30;37(6):e9469. doi: 10.1002/rcm.9469.

DOI:10.1002/rcm.9469
PMID:36593223
Abstract

RATIONALE

Nasopharyngeal carcinoma (NPC) is a malignant tumor that is endemic in Southeast Asia, North Africa, and southern China. There is an urgent need for effective early diagnosis and treatment of this disease since NPC is currently often detected at advanced stages.

METHODS

To reveal the underlying metabolic mechanisms and discover potential diagnostic biomarkers of NPC, we employed ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and UHPLC-Q-Exactive Orbitrap MS, respectively, to analyze 54 serum samples and 54 urine samples from 27 patients with NPC and 27 healthy control individuals.

RESULTS

A total of 1230 metabolites were determined in serum samples, and 181 of the 1230 metabolites were significantly changed in NPC patients. The 181 metabolites were enriched in 16 pathways, including biosynthesis of unsaturated fatty acids, cholesterol metabolism, and ferroptosis. A total of 2509 metabolites were detected in the urine samples. Among them, 179 metabolites were significantly altered in NPC patients, and these metabolites were enriched in eight pathways, including the tricarboxylic acid (TCA) cycle and caffeine metabolism. Seven metabolites, including creatinine and paraxanthine, were found to be significantly changed in both NPC serum and urine samples. Based on them, further biomarker analysis revealed that the panel of three serum metabolites, octanoylcarnitine, creatinine, and decanoyl-l-carnitine, displayed a perfect diagnostic performance (area under the curve [AUC] = 0.973) to distinguish NPC patients from controls, while the other three-metabolite biomarker panel, consisting of stachydrine, decanoyl-l-carnitine, and paraxanthine, had an AUC = 0.809 to distinguish NPC and control in urine samples.

CONCLUSION

This work highlights the key metabolites and metabolic pathways disturbed in NPC and presents potential biomarkers for effective diagnosis of this disease.

摘要

原理

鼻咽癌(NPC)是一种在东南亚、北非和中国南方地区高发的恶性肿瘤。由于鼻咽癌目前常在晚期才被发现,因此迫切需要有效的早期诊断和治疗方法。

方法

为揭示鼻咽癌潜在的代谢机制并发现潜在的诊断生物标志物,我们分别采用超高效液相色谱联用四极杆飞行时间质谱(UHPLC-Q-TOF-MS)和UHPLC-Q-Exactive Orbitrap质谱,对27例鼻咽癌患者和27例健康对照者的54份血清样本和54份尿液样本进行分析。

结果

在血清样本中总共测定了1230种代谢物,其中181种代谢物在鼻咽癌患者中发生了显著变化。这181种代谢物富集在16条通路中,包括不饱和脂肪酸的生物合成、胆固醇代谢和铁死亡。在尿液样本中总共检测到2509种代谢物。其中,179种代谢物在鼻咽癌患者中发生了显著改变,这些代谢物富集在8条通路中,包括三羧酸(TCA)循环和咖啡因代谢。发现包括肌酐和对黄嘌呤在内的7种代谢物在鼻咽癌血清和尿液样本中均发生了显著变化。基于这些代谢物,进一步的生物标志物分析显示,由辛酰肉碱、肌酐和癸酰-L-肉碱组成的三种血清代谢物组合在区分鼻咽癌患者和对照方面表现出完美的诊断性能(曲线下面积[AUC]=0.973),而由水苏碱、癸酰-L-肉碱和对黄嘌呤组成的另一种三种代谢物生物标志物组合在区分尿液样本中的鼻咽癌和对照方面的AUC=0.809。

结论

这项工作突出了鼻咽癌中受干扰的关键代谢物和代谢通路,并提出了用于有效诊断该疾病的潜在生物标志物。

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