Zhang Su, Lu Xin, Hu Chunxiu, Li Yanli, Yang Huan, Yan Huijiao, Fan Jinhu, Xu Guowang, Abnet Christian C, Qiao Youlin
Department of Cancer Epidemiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 South Panjiayuan Lane, Beijing 100021, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
ACS Omega. 2020 Oct 12;5(41):26402-26412. doi: 10.1021/acsomega.0c02600. eCollection 2020 Oct 20.
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor diagnosis. Esophageal squamous dysplasia (ESD) is considered as an immediate precancerous lesion of ESCC. Lack of biomarkers for discriminating ESCC and ESD from healthy subjects limits the early diagnosis and treatment of ESCC. Therefore, a serum metabolomic strategy was conducted to identify and validate potential metabolic markers for the screening of ESCC and ESD subjects. METHODS: A total of 74 patients with ESCC, 72 patients with ESD, and 75 normal control (NC) subjects were enrolled in this study. Gas chromatography-mass spectrometry was used to acquire serum metabolic profiles. Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC. Multivariate analyses were used to screen and validate the biomarkers. RESULTS: ESCC, ESD, and NC subjects revealed progressively altered metabolic profiles, in which amino acids globally increased, while fatty acids decreased in ESCCs compared with the control groups. Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids. The panel constructed with propanoic acid, linoleic acid, glycerol-3-phosphate, and l-glutamine showed the area under the curve (AUC), sensitivity, and specificity of 0.817, 0.75, and 0.74, respectively, in the discrimination of ESCC/ESD patients from NC subjects. The panel constructed by propanoic acid, l-leucine, and hydroxyproline revealed the AUC, sensitivity, and specificity of 0.819, 0.76, and 0.72, respectively, in the discrimination of ESD from NC subjects. The combination of hypoxanthine, 2-ketoisocaproic acid, l-glutamate, and l-aspartate showed the AUC, sensitivity, and specificity of 0.818, 0.83, and 0.74, respectively, in the discrimination of ESCC patients from ESD subjects. CONCLUSIONS: Our study revealed the systematic landscape for metabolic alterations in sera of ESD and ESCC patients. The defined metabolite markers showed reasonable performance in the discrimination of ESCC and ESD patients, and may provide helpful reference for clinicians and biologists.
背景：食管鳞状细胞癌（ESCC）是最常见的恶性肿瘤之一，诊断困难。食管鳞状上皮发育异常（ESD）被认为是ESCC的直接癌前病变。缺乏用于区分ESCC和ESD与健康受试者的生物标志物限制了ESCC的早期诊断和治疗。因此，开展了一项血清代谢组学策略，以识别和验证用于筛查ESCC和ESD受试者的潜在代谢标志物。 方法：本研究共纳入74例ESCC患者、72例ESD患者和75例正常对照（NC）受试者。采用气相色谱-质谱联用技术获取血清代谢谱。进行通路分析以揭示ESCC过程中波动的代谢通路。采用多变量分析来筛选和验证生物标志物。 结果：ESCC、ESD和NC受试者的代谢谱呈现出逐渐改变的趋势，其中与对照组相比，ESCC患者体内氨基酸整体增加，而脂肪酸减少。通路分析表明氨基酸生物合成被激活，饱和脂肪酸去饱和作用受到抑制。由丙酸、亚油酸、3-磷酸甘油和L-谷氨酰胺构建的指标在区分ESCC/ESD患者与NC受试者时，曲线下面积（AUC）、敏感性和特异性分别为0.817、0.75和0.74。由丙酸、L-亮氨酸和羟脯氨酸构建的指标在区分ESD与NC受试者时，AUC、敏感性和特异性分别为0.819、0.76和0.72。次黄嘌呤、2-酮异己酸、L-谷氨酸和L-天冬氨酸的组合在区分ESCC患者与ESD受试者时，AUC、敏感性和特异性分别为0.818、0.83和0.74。 结论：我们的研究揭示了ESD和ESCC患者血清中代谢改变的系统概况。确定的代谢物标志物在区分ESCC和ESD患者方面表现出合理的性能，可能为临床医生和生物学家提供有用的参考。
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