Metabonomic Studies of Human Hepatocellular Carcinoma Using High-Resolution Magic-Angle Spinning ¹H NMR Spectroscopy in Conjunction with Multivariate Data Analysis

Abstract

High-resolution magic-angle spinning (MAS) 1H nuclear magnetic resonance spectroscopy has been employed to characterize the metabolite composition (i.e., metabonome) of the human hepatocellular carcinoma (HCC) tumor in combination with principal component analysis (PCA). The results showed that (a) the metabonomes of both low-grade HCC and high-grade HCC tumors differ markedly from that of the adjacent non-involved tissues; and (b) low-grade HCC tumors have clear differences in metabonome from that of the high-grade HCC tumors. Compared with the non-involved adjacent liver tissues, HCC tumors had elevated levels of lactate, glutamate, glutamine, glycine, leucine, alanine, choline metabolites, and phosphorylethanolamine (PE), but declined levels of triglycerides, glucose, and glycogen. The levels of lactate, amino acids including glutamate, glutamine, glycine, leucine and alanine, choline and phosphorylethanolamine (PE) were higher but the levels of PC, GPC, triglycerides, glucose, and glycogen were lower in high-grade HCC than in low-grade HCC tumors. Compared with non-cirrhotic, low-grade HCC tumors, the cirrhotic, low-grade HCC tumors showed statistically significant increases in lactate, phosphocholine (PC), and glycerophosphocholine (GPC). The necrosis in HCC tumors resulted in a drastic increase in the levels of observable triglycerides, signals of which dominated their 1H NMR spectra. These results indicated that HRMAS combined with PCA offers a useful tool for understanding the tumor biochemistry and classification of liver tumor tissues; such tool may also have some potential for liver tumor diagnosis and prognosis even when some other disease processes are present.

Tissue metabolomic fingerprinting reveals metabolic disorders associated with human gastric cancer morbidity

“…It has been reported that cancer cells predominantly produce energy by glycolysis rather than oxidative phosphorylation via the tricarboxylic acid (tCA) cycle (38). promotion of glycolysis and disruption of the tCA cycle were also noted in invasive ovarian carcinoma (32), liver cancer (39) and colorectal cancer (40). Abnormal metabolism of carbohydrates may be associated with tumor growth with a large energy requirement needed for aggressive cell proliferation.…”

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…Moreover, glutamine synthetase expression is correlated with HCC progression [93,96]. Supporting the importance of glutamine metabolism in liver cancer, increased concentrations of glutamate and glutamine have been detected in human HCC in comparison to adjacent normal tissue [97]. Interestingly, glutamine synthethase expression is related to liver regeneration and therefore is observed during cirrhosis (a pre-state of liver cancer) [93,98].…”

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

“…Five metabolites quinaldic acid, β-sitosterol, arachidyl carnitine, oleamide and tetradecanal were observed for the first time. Nine metabolite lysophosphatidylethanolamines, glycerophosphocholine, LPCs, CDCA glycine conjugate and Lphenylalanine had been reported as serum metabolite biomarkers for HCC diagnosis in previous research [39][40][41].…”