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Identification of serum biomarkers of hepatocarcinoma through liquid chromatography/mass spectrometry-based metabonomic method

机译:基于液相色谱/质谱的代谢组学方法鉴定肝癌血清生物标志物

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摘要

Late diagnosis of hepatocarcinoma (HCC) is one of the most primary factors for the poor survival of patients. Thereby, identification of sensitive and specific biomarkers for HCC early diagnosis is of great importance in biological medicine to date. In the present study, serum metabolites of the HCC patients and healthy controls were investigated using the improved liquid chromatography–mass spectrometry (LC/MS). A wavelet-based method was utilized to find and align peaks of LC–MS. The characteristic peaks were selected by performing a two-sample t test statistics (p value <0.05). Clustering analysis based on principal component analysis showed a clear separation between HCC patients and healthy individuals. The serum metabolite, namely 1-methyladenosine, was identified as the characteristic metabolite for HCC. Moreover, receiver–operator curves were calculated with 1-methyladenosine and/or alpha fetal protein (AFP). The higher area under curve value was achieved in 1-methyladenosine group than AFP group (0.802 vs. 0.592), and the diagnostic model combining 1-methyladenosine with AFP exhibited significant improved sensitivity, which could identify those patients who missed the diagnosis of HCC by determining serum AFP alone. Overall, these results suggested that LC/MS-based metabonomic study is a potent and promising strategy for identifying novel biomarkers of HCC.
机译:肝癌(HCC)的晚期诊断是患者生存不良的最主要因素之一。因此,迄今为止,鉴定用于肝癌早期诊断的敏感和特异性生物标志物在生物医学中非常重要。在本研究中,使用改良的液相色谱-质谱法(LC / MS)对HCC患者和健康对照组的血清代谢产物进行了研究。基于小波的方法用于查找和对齐LC-MS的峰。通过执行两次样本t检验统计量选择特征峰(p值<0.05)。基于主成分分析的聚类分析表明,HCC患者与健康个体之间存在明显的分离。血清代谢物,即1-甲基腺苷,被确定为肝癌的特征代谢物。此外,用1-甲基腺苷和/或α胎儿蛋白(AFP)计算出接收者-操作者曲线。 1-甲基腺苷组的曲线下面积高于AFP组(0.802 vs. 0.592),并且1-甲基腺苷与AFP组合的诊断模型显示出显着提高的敏感性,从而可以通过仅测定血清AFP。总体而言,这些结果表明,基于LC / MS的代谢组学研究是鉴定HCC新型生物标志物的有效且有前途的策略。

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