Liu Ran, Peng Yuan, Li Xiaobo, Wang Yi, Pan Enchun, Guo Wei, Pu Yuepu, Yin Lihong
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
Int J Mol Sci. 2013 Apr 24;14(5):8899-911. doi: 10.3390/ijms14058899.
Epidemiological studies indicated that esophageal squamous-cell carcinoma (ESCC) is still one of the most common causes of cancer incidence in the world. Searching for valuable markers including circulating endogenous metabolites associated with the risk of esophageal cancer, is extremely important A comparative metabolomics study was performed by using ultraperformance liquid chromatography-electrospray ionization-accurate mass time-of-flight mass spectrometry to analyze 53 pairs of plasma samples from ESCC patients and healthy controls recruited in Huaian, China. The result identified a metabolomic profiling of plasma including 25 upregulated metabolites and five downregulated metabolites, for early diagnosis of ESCC. With a database-based verification protocol, 11 molecules were identified, and six upregulated molecules of interest in ESCC were found to belong to phospholipids as follows: phosphatidylserine, phosphatidic acid, phosphatidyl choline, phosphatidylinositol, phosphatidyl ethanolamine, and sphinganine 1-phosphate. Clinical estimation of metabolic biomarkers through hierarchical cluster analysis in plasma samples from 17 ESCC patients and 29 healthy volunteers indicated that the present metabolite profile could distinguish ESCC patients from healthy individuals. The cluster of aberrant expression of these metabolites in ESCC indicates the critical role of phospholipid metabolism in the oncogenesis of ESCC and suggests its potential ability to assess the risk of ESCC development in addition to currently used risk factors.
流行病学研究表明,食管鳞状细胞癌(ESCC)仍是全球癌症发病的最常见原因之一。寻找包括与食管癌风险相关的循环内源性代谢物在内的有价值标志物极为重要。我们采用超高效液相色谱 - 电喷雾电离 - 精确质量飞行时间质谱法,对在中国淮安招募的53对ESCC患者和健康对照的血浆样本进行了比较代谢组学研究。结果确定了血浆的代谢组学图谱,包括25种上调代谢物和5种下调代谢物,用于ESCC的早期诊断。通过基于数据库的验证方案,鉴定出11种分子,发现ESCC中6种上调的感兴趣分子属于磷脂,如下所示:磷脂酰丝氨酸、磷脂酸、磷脂酰胆碱、磷脂酰肌醇、磷脂酰乙醇胺和鞘氨醇1 - 磷酸。通过对17例ESCC患者和29名健康志愿者的血浆样本进行层次聚类分析,对代谢生物标志物进行临床评估,结果表明当前的代谢物谱可以区分ESCC患者和健康个体。这些代谢物在ESCC中的异常表达聚类表明磷脂代谢在ESCC肿瘤发生中的关键作用,并表明其除了目前使用的风险因素外,还具有评估ESCC发生风险的潜在能力。