A Large-scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma.
A Large-scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma.
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DOI：
10.1002/hep.29561
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Luo P;Yin P;Hua R;Tan Y;Li Z;Qiu G;Yin Z;Xie X;Wang X;Chen W;Zhou L;Wang X;Li Y;Chen H;Gao L;Lu X;Wu T;Wang H;Niu J;Xu G
肝细胞癌（HCC）是全球第三大致死性癌症。缺乏有效的生物标志物用于早期检测HCC导致治愈性治疗不令人满意。在这里，代谢物生物标志物被鉴定并验证用于HCC诊断。从中国多个中心共招募了1，448例受试者，包括健康对照和慢性B型肝炎病毒感染、肝硬化和HCC患者。基于液相色谱-质谱的代谢组学方法被用来表征受试者的血清代谢谱，并筛选和验证HCC生物标志物。定义了包括苯丙氨酰-色氨酸和甘胆酸盐的血清代谢物生物标志物组。在区分HCC与肝硬化高危人群方面，该组的诊断性能高于甲胎蛋白（AFP），例如该组的受试者工作特征曲线下面积为0.930、0.892和0.807，而在验证集的发现集、测试集和队列1中，AFP的受试者工作特征曲线下面积为0.657、0.725和0.650，分别在巢式病例对照研究中，该试剂盒检测临床前HCC的灵敏度较高（范围为80.0%-70.3%），与AFP联合使用可在临床诊断前更好地预测临床前HCC的风险。此外，在区分小HCC方面，该面板显示出比AFP更大的受试者工作特征曲线下面积（0.866 vs 0.682），并且在测试集中使用该面板正确诊断了80.6%的AFP假阴性HCC患者，这得到了验证集的证实。分别使用来自另外两种癌症和HCC组织标本的血清进一步评价鉴定的生物标志物的特异性和生物相关性。结论：发现和验证的血清代谢物生物标志物组在高危人群中早期检测HCC方面表现出良好的诊断性能。（Hepatology 2018;67：662 - 675）。
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 patients with HCC were correctly diagnosed using this panel in the test set, which was corroborated by the validation set. The specificity and biological relevance of the identified biomarkers were further evaluated using sera from another two cancers and HCC tissue specimens, respectively. Conclusion: The discovered and validated serum metabolite biomarker panel exhibits good diagnostic performance for the early detection of HCC from at‐risk populations. (Hepatology 2018;67:662‐675).
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影响因子：
4.6
作者：
Liang Q;Liu H;Wang C;Li B
通讯作者：
Li B
影响因子：
51.1
作者：
Oberg, Kjell;Modlin, Irvin M.;De Herder, Wouter;Pavel, Marianne;Klimstra, David;Frilling, Andrea;Metz, David C.;Heaney, Anthony;Kwekkeboom, Dik;Strosberg, Jonathan;Meyer, Timothy;Moss, Steven F.;Washington, Kay;Wolin, Edward;Liu, Eric;Goldenring, James
通讯作者：
Goldenring, James
DOI：
10.1111/liv.12541
发表时间：
2014-10
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
--
作者：
Fitian AI;Nelson DR;Liu C;Xu Y;Ararat M;Cabrera R
通讯作者：
Cabrera R
影响因子：
50.3
作者：
Kettner NM;Voicu H;Finegold MJ;Coarfa C;Sreekumar A;Putluri N;Katchy CA;Lee C;Moore DD;Fu L
通讯作者：
Fu L
影响因子：
45.3
作者：
Altekruse, Sean F.;McGlynn, Katherine A.;Reichman, Marsha E.
通讯作者：
Reichman, Marsha E.