Liquid Chromatography-Mass Spectrometry-Based Nontargeted Metabolomics Predicts Prognosis of Hepatocellular Carcinoma after Curative Resection
Liquid Chromatography-Mass Spectrometry-Based Nontargeted Metabolomics Predicts Prognosis of Hepatocellular Carcinoma after Curative Resection
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基于液相色谱-质谱分析的非靶向代谢组学预测肝细胞癌根治性切除后的预后
DOI：
10.1021/acs.jproteome.0c00344
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发表时间：
2020
影响因子：
4.4
通讯作者：
Xu Guowang
中科院分区：
文献类型：
--
作者：
Wang Qingqing;Su Benzhe;Dong Liwei;Jiang Tianyi;Tan Yexiong;Lu Xin;Liu Xinyu;Lin Xiaohui;Xu Guowang
对肝细胞癌（HCC）患者预后风险的评估和预测，将大大有利于最佳治疗方案的选择。在这里，我们的目的是确定与结果相关的关键代谢物，并制定一个风险评分，以评估肝癌患者根治性切除术后的预后。共78例HCC患者的血清样本进行了分析，通过液相色谱-质谱法来表征代谢谱。提出了一种新的基于网络的特征选择方法（NFSM），用于确定对结果具有最大区分能力的关键代谢物。通过考克斯回归分析进一步减少NFSM定义的代谢物，以生成预测代谢物组-苯丙氨酸和胆碱。此外，应用单变量和多变量考克斯回归分析，将代谢物组与卫星节点的存在结合联合收割机，以生成用于总生存期评估的总体预后指数（GPI）评分。根据时间依赖性受试者工作特征曲线，GPI评分与当前临床分类系统（包括HCC临床分期、肿瘤淋巴结转移分期和白蛋白胆红素分级）相比具有相当的性能，并在独立队列中得到验证，这表明代谢组学可以作为HCC术后预后风险分层的有用工具。
Assessment and prediction of prognostic risk in patients with hepatocellular carcinoma (HCC) would greatly benefit the optimal treatment selection. Here, we aimed to identify the critical metabolites associated with the outcomes and develop a risk score to assess the prognosis of HCC patients after curative resection. A total of 78 serum samples of HCC patients were analyzed by liquid chromatography–mass spectrometry to characterize the metabolic profiling. A novel network-based feature selection method (NFSM) was developed to define the critical metabolites with the most discriminant capacity to outcomes. The metabolites defined by NFSM was further reduced by Cox regression analysis to generate a prognostic metabolite panel—phenylalanine and choline. Furthermore, univariate and multivariate Cox regression analyses were applied to combine the metabolite panel with the presence of satellite nodes to generate a global prognostic index (GPI) score for overall survival assessment. Compared with the current clinical classification systems, including the Barcelona-clinic liver cancer stage, tumor–node–metastasis stage, and albumin–bilirubin grade, the GPI score presented comparable performance, according to the time-dependent receiver operating characteristic curves and was validated in an independent cohort, which suggested that metabolomics could serve as a helpful tool to stratify the HCC prognostic risk after operation.