Circulating Metabolic Markers Related to the Diagnosis of Hepatocellular Carcinoma

Primary liver carcinoma is the sixth most common cancer worldwide, while hepatocellular carcinoma (HCC) is the most dominant cancer type. Chronic hepatitis B and C virus infections and aflatoxin exposure are the main risk factors, while nonalcoholic fatty liver disease caused by obesity, diabetes, and metabolic syndrome are the more common risk factors for HCC. Metabolic disorders caused by these high-risk factors are closely related to the tumor microenvironment of HCC, revealing a possible cause-and-effect relationship between the two. These metabolic disorders involve many complex metabolic pathways, such as carbohydrate, lipid, lipid derivative, amino acid, and amino acid derivative metabolic processes. The resulting metabolites with significant abnormal changes in the concentration level in circulating blood may be used as biomarkers to guide the diagnosis, treatment, or prognosis of HCC. At present, there are high-throughput technologies that can quickly detect small molecular metabolites in many samples. Compared to tissue biopsy, blood samples are easier to obtain, and patients' willingness to participate is higher, which makes it possible to study blood HCC biomarkers. Over the past few years, a substantial body of research has been performed worldwide, and other potential biomarkers have been identified. Unfortunately, due to the limitations of each study, only a few markers have been widely verified and are suitable for clinical use. This review briefly summarizes the potential blood metabolic markers related to the diagnosis of HCC, mainly focusing on amino acids and their derivative metabolism, lipids and their derivative metabolism, and other possible related metabolisms.