A Large‐scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma

作者：Ping Luo, Peiyuan Yin, Rui Hua, Yexiong Tan, Zaifang Li, Gaokun Qiu, Zhenyu Yin, Xingwang Xie, Xiaomei Wang, Wenbin Chen, Lina Zhou, Xiaolin Wang, Yanli Li, Hongsong Chen, Ling Gao, Xin Lu, Tangchun Wu, Hongyang Wang, Junqi Niu, Guowang Xu · 发表于：Hepatology · 年份：2017 · DOI：10.1002/hep.29561 · 被引用次数：380 · 研究领域：Liver Disease Diagnosis and Treatment、Metabolomics and Mass Spectrometry Studies、Hepatocellular Carcinoma Treatment and Prognosis

Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. The lack of effective biomarkers for the early detection of HCC results in unsatisfactory curative treatments. Here, metabolite biomarkers were identified and validated for HCC diagnosis. A total of 1,448 subjects, including healthy controls and patients with chronic hepatitis B virus infection, liver cirrhosis, and HCC, were recruited from multiple centers in China. Liquid chromatography-mass spectrometry-based metabolomics methods were used to characterize the subjects' serum metabolic profiles and to screen and validate the HCC biomarkers. A serum metabolite biomarker panel including phenylalanyl-tryptophan and glycocholate was defined. This panel had a higher diagnostic performance than did α-fetoprotein (AFP) in differentiating HCC from a high-risk population of cirrhosis, such as an area under the receiver-operating characteristic curve of 0.930, 0.892, and 0.807 for the panel versus 0.657, 0.725, and 0.650 for AFP in the discovery set, test set, and cohort 1 of the validation set, respectively. In the nested case-control study, this panel had high sensitivity (range 80.0%-70.3%) to detect preclinical HCC, and its combination with AFP provided better risk prediction of preclinical HCC before clinical diagnosis. Besides, this panel showed a larger area under the receiver-operating characteristic curve than did AFP (0.866 versus 0.682) to distinguish small HCC, and 80.6% of the AFP false-negative pa...