Metabolomics Study of Stepwise Hepatocarcinogenesis From the Model Rats to Patients: Potential Biomarkers Effective for

The aim of this study is to find the potential biomarkers from the rat hepatocellular carcinoma (HCC) disease model by using a non-target metabolomics method, and test their usefulness in early human HCC diagnosis. The serum met-abolic profiling of the diethylnitrosamine-induced rat HCC model, which presents a stepwise histopathological pro-gression that is similar to human HCC, was performed us-ing liquid chromatography-mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. Three metabolites, taurocholic acid, lysophos-phoethanolamine 16:0, and lysophosphatidylcholine 22:5, were defined as “marker metabolites, ” which can be used to distinguish the different stages of chemical hepatocarci-nogenesis. These metabolites represented the abnormal metabolism during the progress of hepatocarcinogenesis, which could also be found in patients. To test their diagno-sis potential 412 sera from 262 patients with HCC, 76 pa-tients with cirrhosis and 74 patients with chronic hepatitis B were collected and studied, it was found that 3 marker metabolites were effective for the discrimination of small liver tumor (solitary nodules of less than 2 cm in diameter) patients, achieved a sensitivity of 80.5 % and a specificity of 80.1%,which is better than those of -fetoprotein (53 and 64%, respectively). Moreover, they were also effective for the discrimination of all HCCs and chronic liver disease patients, which could achieve a sensitivity of 87.5 % and a specificity of 72.3%, better than those of -fetoprotein (61.2 and 64%). These results indicatemetabolomicsmethod has the potential of finding biomarkers for the early diagnosis o