Metabolomic Analysis For Diagnosis And Prognosis Of Hepatocellular Carcinoma

Objective Hepatocellular carcinoma is one of the most common malignant tumors in China,and it is the third most fatal malignant tumors in the world.Early hepatocellular carcinoma has no specific clinical symptoms,no obvious positive signs or only similar to liver cirrhosis signs.When obvious clinical symptoms and signs appear,hepatocellular carcinoma is in the middle or late stage,which greatly affect the cure rate and prognosis.Metabolomics as an important branch of system biology is a newly developed subject after transcriptome and genomics.The principle is to study the overall biological metabolism by analyzing the biological changes of small molecular metabolites in organisms.Metabolomics technology has shown a good application prospect in disease classification,marker discovery,drug toxicity evaluation and so on.Many people have used metabolomics technology to study hepatocellular carcinoma,looking for potential metabolic biomarkers.In this study,by means of metabolomics,the blood samples of 41 patients with hepatocellular carcinoma,48 patients with liver cirrhosis,40 patients with non-recurrence of hepatocellular carcinoma and 41 patients with recurrence of hepatocellular carcinoma were analyzed by DBS direct injection mass spectrometry.Screening out the differential metabolites to assist diagnosis and determine the prognosis of hepatocellular carcinoma,hoping to provide a new idea for the diagnosis and prognosis of hepatocellular carcinoma.Methods 1.Research object and experimental grouping: 170 patients in our hospital(including 41 patients with first confirmed liver cancer,48 patients with clinically confirmed liver cirrhosis,41 patients with recurrent liver cancer and 40 patients with non-recurrent liver cancer after treatment)were selected and divided into three experimental groups.Experimental group 1 consisted of 41 patients with liver cancer diagnosed for the first time and 48 patients with clinically diagnosed liver cirrhosis.The experimental group 2 consisted of 41 patients with no recurrence of liver cancer after treatment and 40 patients with recurrence of liver cancer.The experimental group 3 consisted of 48 patients with liver cirrhosis and 41 patients with recurrent liver cancer.Diagnostic criteria refer to the guidelines for diagnosis and treatment of primary liver cancer issued by the general office of the national health and family planning Commission in 2017,and the whole blood samples of the above subjects are collected.2.Experimental method: Direct Injection Mass Spectrometry Metabolomics Method Based on Dry Blood Drops(DBS).The target metabolite detected consists of 23 amino acids and 26 acylcarnitine.3.The experimental results were extracted and pretreated,and then the compounds were qualitatively and quantitatively analyzed by spectral library retrieval.Then the data were analyzed by partial least squares discriminant analysis(PLS-DA)model.After analyzing the data,the differential metabolites were found,and the binary Logistic regression analysis model was constructed,the discriminant ability of differential metabolites was verified by ROC curve.Result 1.Through Multivariate analysis: 10 detection molecules(three amino acids Ala,Orn,Ser and seven carnitines(C4-OH,C4,C5,C5-OH,C10,C10:1,C14:1)and two ratios C4/C3,Orn/Cit were higher in liver cancer group.However,the four detection molecules C16:1-OH,C18,C22,C24 and the two ratios C5DC/C5-OH,Gly/Ala in liver cancer group are higher than those in liver cirrhosis group.2.Through Multivariate analysis: Six differential metabolites were found between the non-recurrence group and the recurrence group.Based on the regression analysis of these seven metabolites,a diagnostic model was established to determine whether liver cancer recurred or not.3.Multivariate analysis showed that there were 13 different metabolites and 6 abnormal ratios between patients with liver cirrhosis and patients with liver cancer.Conclusion Metabolomics method can provide new biomarkers for early diagnosis and prognosis evaluation of liver cancer,and provide new technical means for diagnosis and prognosis evaluation of liver cancer.