Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Abstract

In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1

“…Identifying the key genes maintaining the malignant phenotype would be of great significant for molecular targeted therapy of HCC. Abnormally active of lipid synthesis was observed in HCC pathophysiology ( 20 ). However, it was still unclear how these lipid synthesis enzymes contribute to the progression of HCC.…”

Updates on the Diagnosis and Management of Hepatocellular Carcinoma

“… 42 There is growing interest in the role of metabolomics in predicting early HCC, and metabolomics studies have been carried out in common liver disorders like alcoholic liver disease, cirrhosis, and nonalcoholic fatty liver disease. 43 It is expected that such studies may be useful in decreasing the occurrence of HCC in at-risk population.…”

Six Metabolism Related mRNAs Predict the Prognosis of Patients With Hepatocellular Carcinoma

“…Recent years have seen a gradual increase in the number of reports on the use of genomics, proteomics and metabolomics technology to study the pathogenesis and tumorigenesis of malignant tumors ( Kimhofer et al, 2015 ; De Stefano et al, 2018 ; Beyoglu and Idle, 2020 ). Since metabolic disorder is a key event in the occurrence and development of HCC, HCC has been considered a type of metabolic disease ( Piccinin et al, 2019 ).…”