Plasma metabolomic analysis of human hepatocellular carcinoma: Diagnostic and therapeutic study

Abstract

Many hepatocellular carcinoma (HCC) patients suffer from late stages when diagnosed, leading to dismal prospects for cure. Improving the diagnosis and treatment of HCC remains a challenge. In this work, NMR-based metabolomic techniques were used to investigate the metabolic alterations of HCC patients from different pathological backgrounds. Metabolic improvement of clinical surgical treatments or transcatheter arterial chemoembolization (TACE) for recurrent or metastatic HCC was also evaluated. HCC was characterized by enhanced lipid metabolism and high consumption in response to liver injury. Expectedly, higher consumption of glucose and lactate production in TACE group confirmed that recurrent or metastatic HCC is more active in citric acid cycle and oxidative phosphorylation. However, TACE or surgical treatments did not immediately improve the metabolic profiles of HCC patients. Combining multivariate statistical analyses with univariate t-test, a series of characteristic metabolites were identified and served as biomarkers for discrimination of HCC patients in different pathological backgrounds. The relative metabolic pathway analyses help to get insight into the underlying biochemical mechanism and extend clinical relevance. Furthermore, algorithm of support vector classification was used to identify HCC and control subjects, and diagnostic sensitivity and specificity reached to 100% and 81.08% respectively by receiver operating characteristic analysis. It is concluded that NMR-based metabolomic analysis of plasma can provide a powerful approach to discover diagnostic and therapeutic biomarkers, and subsequently contribute to clinical disease management.

Aberrant Metabolism in Hepatocellular Carcinoma Provides Diagnostic and Therapeutic Opportunities

“…This confirms the glycolytic shift toward lactate and provides a correlation between enzymatic alterations and metabolite expression [ 46 ]. The increased lactate concentration observed in the serum of HCC patients, compared to normal subjects, seems to be a consequence of this metabolic change [ 47 ]. However, the role of this secreted lactate still remains largely unclear.…”

1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages

“…The differences in the metabolite patterns were studied by the analysis of the corresponding S-line plot (Figure 2b). From the analysis, a relative lower level of lactate (loadings corresponding to the NMR signals at 1.34 and 4.14 ppm) was observed in ADV with respect to EAR HCC patients [6]. Moreover, a relative higher level of αand β-glucose was found in ADV with respect to EAR HCC patients.…”

“…In the last few years, metabolite quantification by Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy approaches have been used to obtain a global, unbiased view of small molecules in biofluids and organs, thus contributing to the understanding of the molecular characteristics of many diseases. Moreover, these approaches were also used to define a series of biomarkers for early diagnoses and treatments of different diseases [6][7][8][9]. In this study, the serum of 64 HCC patients diagnosed in early (28 patients) and advanced (36 patients) disease stages was collected and profiled by the 1 H-Nuclear Magnetic Resonance ( 1 H-NMR)-based metabolomics approach coupled with multivariate data analysis.…”

Biomarkers vs imaging in the early detection of hepatocellular carcinoma and prognosis

“…HCC is characterized by aerobic glycolysis, increased consumption of glucose, and high levels of lactate. This type of metabolism persists immediately following surgery or transcatheter arterial chemoembolization, as demonstrated by Chen et al[89]. Kim et al[90] studied the molecular changes produced by alteration in the energy metabolism pathways that underlie the metabolomic and proteomic observations, in order to better determine their practical application in the early detection of HCC.…”