Mongolian HCC vs. Caucasian HCC: The Metabolic Reprogramming Process in Mongolian HCC is an Interesting Difference.

Abstract

Racial/ethnic and region disparities in incidence and mortality are obviously in liver cancer. Mongolia has the highest reported incidence and mortality of hepatocellular carcinoma (HCC) in the world, while the incidence of HCC is relatively low in the United States, but differences in their molecular characteristics remain largely elusive. Here we report differentially expressed genes (DEGs) in Mongolian hepatocellular carcinoma and in Caucasian HCC and their intersection DEGs, as well as their corresponding signaling pathways in Mongolian and Caucasian hepatocellular carcinoma patients based on the transcriptome sequences from Gene Expression Omnibus (GEO) database. We got 908 up-regulated genes and 1946 down-regulated genes in Mongolian HCC, 1244 up-regulated genes and 1912 down-regulated genes in Caucasian HCC, 254 Co-upregulated genes and 1035 co-downregulated genes in Mongolian and Caucasian. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that most of the genes with altered expression levels in Mongolian HCC participate in biological processes that involve metabolic reprogramming of various substances, accounting for about one-third of all biological processes. In particular, multiple amino acid biosynthesis and metabolic processes appear to be specific in Mongolian HCC compared with Caucasian HCC. The biological processes they share include those in which most immune cells are involved and cell cycle-related biological processes. In addition, we also found the genes UPP2, PCK1, GLYAT, GNMT, ADH1B and HPD, encode for key metabolic enzymes, whose expression level up-regulated or down-regulated more than 5 times in Mongolian HCC and was dramatically correlated with survival in Mongolian HCC (p value < 0.01), More importantly, these molecules are potential targets for some metabolic antitumor drugs. This study not only makes up for the shortcomings of previous studies on liver cancer, which paid more attention to its commonality, but ignored the specificity of liver cancer in different races and regions. More importantly, the purpose of this study is to identify robust molecular subclasses and information with underlying unique tumor biology. And this study may have important implications for the study of the pathogenic factors and molecular mechanisms of hepatocellular carcinoma and the precise therapy of Mongolian HCC.