Serum Metabolic Profiling Research Of HBV-related Hepatocellular Carcinoma Patients Based On LC-MS

Objective To explore metabolic profiling of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) based on liquid chromatography/mass spectrometry(LS/MS), establish differentiating model, select and identify characteristic metabolites. And then to evaluate the clinical value in diagnosing and staging HBV-related HCC, in diagnosing hepatitis C virus(HCV)-related HCC, and in distinguishing other cancers and liver diseases. To analyze the relationship between characteristic metabolites and HBV-related HCC aiming at providing information on metabonomics for revealing the pathogenesis of HBV-related HCC.Methods A total of 311 inpatients and outpatients of Tianjin Third Central Hospital were enrolled in this study, including 126 in HBV group, 45 in HCV group, 115 in differentiation group and 25 in normal group. HBV group included 27 patients with HBV-related hepatitis with DNA negative, 24 HBV-related hepatitis with DNA positive, 24 HBV-related liver cirrhosis, 27 HBV-related HCC treated by surgical removal or radiofrequency, 24 HBV-related HCC treated by intervention. HCV group included 25 patients with HCV-related HCC and 30 HCV-related HCC.Differentiation group included 22 patients with pancreatic cancer, 24 cholangiocarcinoma, 17 lung cancer, 12 gastric cancer, 26 autoimmune liver disease and 14 alcoholic liver disease. Orthogonal partial least-squares discriminant analysis(OPLS-DA) model was established after all the data was pretreated. Basing on HBV group and normal group, metabolites were preliminarily screened. The characteristic metabolites were selected and identified according to the results of non-parametric test. Finally, potential clinical values of identified characteristic metabolites were evaluated by ROC analysis.Results 25 characteristic metabolites were selected and identified including 9 kinds of lysophosphatidylcholines, 2 kinds of fatty acids, 17 ?-estradiol, sphinganine,5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8metabolites with few reports. Comparing with normal group, 22 metabolites with differential expression in HBV-related HCC were found. Comparing with HBV-related liver cirrhosis, 4 metabolites with differential expression in HBV-related HCC were found. Comparing with HBV-related liver cirrhosis, 4 metabolites with differential expression in HBV-related HCC treated by surgical removal or radiofrequency were found. Comparing with HBV-related HCC treated by surgical removal or radiofrequency, 10 metabolites with differential expression in HBV-related HCC treated by intervention were found. Comparing with normal group,20 metabolites with differential expression in HCV-related HCC were found.Comparing with HCV-related liver cirrhosis, 2 metabolites with differential expression in HCV-related HCC were found. Comparing with pancreatic cancer, 12 metabolites with differential expression in HCC were found. Comparing with cholangiocarcinoma, 11 metabolites with differential expression in HCC were found.Comparing with lung cancer, 16 metabolites with differential expression in HCC were found. Comparing with gastric cancer, 8 metabolites with differential expression in HCC were found. Comparing with autoimmune liver disease, 13 metabolites with differential expression in HCC were found. Comparing with alcoholic liver disease, 5metabolites with differential expression in HCC were found. From normal group to HBV-related HCC treated by intervention, many metabolites altered similarly.Comparing with normal group, many metabolites altered similarly both in HBV-related HCC and HCV-related HCC. Comparing with normal group, many metabolites altered similarly in all kinds of cancers, and some altered differently.Conclusions Disease differentiating model was established successfully and characteristic metabolites were selected and identified based on LS/MS. There is a potential clinical value of these metabolites, such as diagnosing and staging HBV-related HCC, diagnosing HCV-related HCC, distinguishing other cancers and distinguishing liver diseases. The same alterations in metabolic pathways may occur in different virus related HCC. The same alterations in metabolic pathways may occur in different kinds of cancers. Different kinds of cancers not only shared the same alterations in metabolic pathways, but also had unique alterations in metabolic pathways. And further studies are needed for verification.