Abstract
Metabolic reprogramming is a hallmark of tumors, including hepatocellular carcinoma (HCC). We used data from The Cancer Genome Atlas and the International Cancer Genome Consortium to assess the alterations in glycolytic and cholesterogenic genes in HCC and to determine their association with clinical features in HCC patients. Based on the gene expression profiles from these databases, we established four subtypes of HCC: cholesterogenic, glycolytic, mixed, and quiescent. The prognosis of the cholesterogenic subgroup was poorer than that of the glycolytic group. Tumors in the glycolytic group were more sensitive to chemotherapy. We also explored the relationships between these metabolic subtypes and previously established HCC subgroups. Glycolytic gene expression correlated strongly with poorer prognostic gene expression in the Hoshida classification of HCC. Whole-genome analyses indicated that aberrant amplification of TP53 and MYC in HCC were associated with abnormal anabolic cholesterol metabolism. The mRNA levels of mitochondrial pyruvate carriers 1 and 2 differed among the HCC metabolic subtypes. In a bioinformatics analysis we identified genomic characteristics of tumor metabolism that varied among different cancer types. These findings demonstrate that metabolic subtypes may be valuable prognostic indicators in HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for 70-90% of cases [1]
Four metabolic subgroups of hepatocellular carcinoma (HCC) were identified based on the dual analysis of glycolytic and cholesterogenic gene expression
610 HCC tumor samples were included in this study (The Cancer Genome Atlas [TCGA], n = 373, and International Cancer Genome Consortium [ICGC], n = 237)
Summary
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for 70-90% of cases [1]. The study of metabolic reprogramming in tumors has developed in recent years, and may provide a new method of eliminating tumor cells effectively [6, 7]. To satisfy the additional energy requirements for their proliferation and growth, tumor cells must reshape their metabolic pathways [8]. Tumor cells differ from normal cells in their metabolism of glucose, amino acids, fatty acids and nucleotides, which provide large amounts of energy and intermediates [9]. The metabolic reprogramming of tumor cells primarily involves hyperactive glycolysis and fatty acid synthesis. Disruptions in certain signaling pathways are known to contribute to metabolic reprogramming in cancer, alterations in glycolipid metabolism have rarely been reported in liver cancer
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