Aberrant Metabolism in Hepatocellular Carcinoma Provides Diagnostic and Therapeutic Opportunities

Abstract

Hepatocellular carcinoma (HCC) accounts for over 80% of liver cancer cases and is highly malignant, recurrent, drug-resistant, and often diagnosed in the advanced stage. It is clear that early diagnosis and a better understanding of molecular mechanisms contributing to HCC progression is clinically urgent. Metabolic alterations clearly characterize HCC tumors. Numerous clinical parameters currently used to assess liver functions reflect changes in both enzyme activity and metabolites. Indeed, differences in glucose and acetate utilization are used as a valid clinical tool for stratifying patients with HCC. Moreover, increased serum lactate can distinguish HCC from normal subjects, and serum lactate dehydrogenase is used as a prognostic indicator for HCC patients under therapy. Currently, the emerging field of metabolomics that allows metabolite analysis in biological fluids is a powerful method for discovering new biomarkers. Several metabolic targets have been identified by metabolomics approaches, and these could be used as biomarkers in HCC. Moreover, the integration of different omics approaches could provide useful information on the metabolic pathways at the systems level. In this review, we provided an overview of the metabolic characteristics of HCC considering also the reciprocal influences between the metabolism of cancer cells and their microenvironment. Moreover, we also highlighted the interaction between hepatic metabolite production and their serum revelations through metabolomics researches.

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

“…Supplementary Materials: The following are available online at http://www.mdpi.com/2072-6694/12/1/241/s1. Figure S1: t[2]/t [3] PCA scoreplot (the first three principal components explained 78.5% of the total variance (R2X= 0.785, Q2=0.698, t[1]= R 2 X= 0.597, Q 2 =0.549, t[2]= R 2 X= 0.116, Q 2 =0.186, t[3]=R 2 X= 0.0723, Q 2 =0.177). (1: hcv, chronic hepatitis C; 2: hbv, chronic hepatitis B; 3: NASH, nonalcoholic steatohepatitis; 4: others)., Figure S2: t[1]/t [2] PCA scoreplot (the first two principal components explained 67% of the total variance (R 2 X= 0.675, Q 2 =0.55, t[1]= R 2 X= 0.51, Q 2 =0.42, t[2]= R 2 X= 0.17, Q 2 =0.22; 1: extrahepatic; 0: no extrahepatic diseases for ADV HCC patients)., Table S1: Classifier Output from Weka analysis, according to Naïve-Bayes classification (Software WEKA 3.8.3, University of Waikato New Zealand), Section S1: NMR measurements, Section S2: NMR data processing and multivariate statistical analyses, Section S3: Tyrosine measure by standard-addition method in the 1 H NMR spectrum.,…”

“…Hence, specific and reliable biomarkers for the early diagnosis and prognosis of HCC can improve the understanding of HCC etiology and allow an early detection of the disease for the reduction of HCC incidence [2]. Altered tumor metabolism is now considered a hallmark of cancer, with diagnostic and therapeutic implications in several cancer types, including HCC [3,4]. An altered metabolic profile supports tumor growth, proliferation and survival by increasing energy production, macromolecular biosynthesis and the maintenance of redox balance [3].…”

“…Altered tumor metabolism is now considered a hallmark of cancer, with diagnostic and therapeutic implications in several cancer types, including HCC [3,4]. An altered metabolic profile supports tumor growth, proliferation and survival by increasing energy production, macromolecular biosynthesis and the maintenance of redox balance [3]. Significant modifications in metabolic pathways have been identified in HCC, and associated with clinical outcomes [5].…”

6-phosphofructo-2-kinase as therapeutic targets in cancer based on an integrated pan-cancer study6-phosphofructo-2-kinase as therapeutic targets in cancer based on an integrated pan-cancer study

“…In the development of cancer, the metabolism ability of cancer cells is abnormal. The exploitation of modulating metabolism of cancer cells may be a potentially therapeutic approach [15][16][17][18]. Development of different therapeutic approaches need to selectively base on glucose consumption.…”

Identification of Mitochondrial-related Prognostic Biomarkers Associated with Metabolic Processes of Hepatocellular Carcinoma

“…Thus, the identi cation of effective biomarkers for HCC-speci c prognosis is urgently needed to improve the management for patients. Recently, global alterations in metabolic pathways were identi ed in HCC [13], providing some new diagnostic and therapeutic opportunities [14]. Taking into account the importance of the alteration of metabolic processes in HCC progression and the highly central position of the mitochondrion in human metabolism, it is essential to identify mitochondrial-related biomarkers for the prognosis of HCC patients, which may also help us to clarify underlying metabolism alterations and identify potential therapeutic drugs, so as to bring new insights into the improvement of the prognosis of HCC patients.…”