Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

Abstract

Patients with chronic liver diseases (CLD) including chronic hepatitis B and hepatic cirrhosis (CIR) are the major high-risk population of hepatocellular carcinoma (HCC). The differential diagnosis between CLD and HCC is a challenge. This work aims to study the related metabolic deregulations in HCC and CLD to promote the discovery of the differential metabolites for distinguishing the different liver diseases. Serum metabolic profiling analysis from patients with CLD and HCC was performed using a liquid chromatography-mass spectrometry system. The acquired large amount of metabolic information was processed with the random forest-recursive feature elimination method to discover important metabolic changes. It was found that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the non-malignant liver diseases, accompanied with corresponding alterations of enzyme activities. However, the general changing extent was smaller in HCC than in CIR, possibly due to the special energy-consumption mechanism of tumor cells. These observations may help to understand the mechanism of HCC occurrence and progression on the metabolic level and provide information for the identification of early and differential metabolic markers for HCC.

UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry

“…Serum metabonomics showed that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the nonmalignant liver diseases, accompanied by the corresponding alterations of the enzyme activities. However, the magnitude of the changes was smaller in HCC than in hepatic cirrhosis, possibly due to the differences in energy metabolism in the tumor cells [33].…”

Lipid Metabolism in Liver Cancer

“…This phonotype was evidenced by the following metabolic changes including the decrease in glucose, citrate, and glycerol 3-phosphate but the increase in lactic acid and pyruvate [64][65][66][67][68][69]. On the other hand, the common induction of beta-oxidation was exemplified by the elevation of 2-oxoglutarate and reduction of free fatty acids, carnitine and carnitine esters [61,64,66,68,[70][71][72][73]. This theme will be further explored in the next section.…”

Postgenomics Diagnostics: Metabolomics Approaches to Human Blood Profiling

“…Recently, metabolomics studies have been used in many fields, such as analyzing the physiologic response to toxicology , nutrition (Lee et al, 2010;Wong and Lodge 2012), and cancer (Lokhov et al, 2010;Sreekumar et al, 2009;Zhou et al, 2012), as well as diabetes and disease diagnosis . The blood metabolome is closely connected with all organs and tissues, and therefore it is convenient and informative for biomarker discovery.…”