Metabolic Characterization of Hepatocellular Carcinoma Using Nontargeted Tissue Metabolomics

Abstract

Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and b-oxidation with reduced tricarboxylic acid cycle and D-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to a-fetoprotein. Cancer Res; 73(16); 4992-5002. Ó2013 AACR.

Acetylcarnitine Is a Candidate Diagnostic and Prognostic Biomarker of Hepatocellular Carcinoma

“…We found long-chain acylcarnitines (>C14) accumulated in hepatocellular carcinoma tumors, whereas short-and medium-chain acylcarnitines decreased. A similar trend of acylcarnitines levels in the liver cancer tissues of hepatocellular carcinoma patients was also observed in a recent study (23). Acylcarnitines play a pivotal role in lipid metabolism in cells (39).…”

“…Current metabolomics studies on hepatocellular carcinoma are mainly focused on identifying significant metabolites in serum/ urine samples with the aim of revealing systemic metabolic changes caused by hepatocellular carcinoma and finding potential biomarkers with clinical application (15)(16)(17)(18)(19)(20)(21)(22). There has been limited analysis of the effects of hepatocellular carcinoma on liver metabolism (23,24). Although serum/urine metabolic profiling can reflect circulating metabolic characterization in hepatocellular carcinoma, targeting ability of these analyses is still limited.…”

Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

“…Metabolomics is defined as the comprehensive and quantitative metabolic analysis of large numbers of endogenous, low-molecular-weight metabolites. In the past decade, the widespread utility of this analytical approach to monitoring multiple metabolic perturbations in living systems within pathological processes [13][14][15][16][17][18][19] , including CKD [17] , and the response to such external stimuli as drug treatments [20,21] has been illustrated. Moreover, this method is now being applied to the field of TCM [22][23][24][25][26] , as it could characterize the subtle metabolic interventions induced by TCM in the treatment of diseases and identify the potential implications of TCM.…”

Lipid Metabolism in Liver Cancer

“…On one hand, the enforced glycolysis over mitochondrial oxygen respiration (also called Warburg effect), although comparatively lower in reaction rates (fourfold increase) than the other types of tumor, was a common metabolic phenotype in tumor. 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].…”