State Key Laboratory of Infectious Disease Diagnosis and Treatment, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Anal Bioanal Chem. 2011 Oct;401(6):1899-904. doi: 10.1007/s00216-011-5245-3. Epub 2011 Jul 22.
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.
肝癌（HCC）的晚期诊断是患者生存率低的最主要因素之一。因此，迄今为止，在生物医学中，寻找和鉴定用于 HCC 早期诊断的敏感和特异的生物标志物具有重要意义。在本研究中，采用改进的液相色谱-质谱法（LC/MS）检测 HCC 患者和健康对照者的血清代谢产物。利用基于小波的方法寻找和对齐 LC-MS 的峰。通过执行双样本 t 检验统计（p 值<0.05）选择特征峰。基于主成分分析的聚类分析显示 HCC 患者和健康个体之间有明显的分离。鉴定出血清代谢产物 1-甲基腺苷为 HCC 的特征代谢产物。此外，计算了基于 1-甲基腺苷和/或甲胎蛋白（AFP）的接收者操作特征曲线。与 AFP 组相比，1-甲基腺苷组的曲线下面积值更高（0.802 对 0.592），且联合 1-甲基腺苷和 AFP 的诊断模型表现出显著提高的灵敏度，这可以通过确定血清 AFP 来识别那些单独 AFP 检测漏诊的 HCC 患者。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。
