Huang Rui, Yang Kun, Zhang Zejuan, Song Lei, Dong Kaizhong, Xie Xiaofeng, Hai Xiangjun
Key Laboratory of Environmental Ecology and Population Health in Northwest Minority Areas, Northwest Minzu University, Lanzhou, 730030, China.
Lanzhou University Second Hospital, Lanzhou, 730030, China.
Biochem Genet. 2024 Jun;62(3):2279-2295. doi: 10.1007/s10528-023-10527-1. Epub 2023 Oct 31.
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.
肝癌在发病率和死亡率方面存在明显的种族/民族及地区差异。据报道，蒙古国的肝细胞癌（HCC）发病率和死亡率在全球最高，而美国的HCC发病率相对较低，但其分子特征差异在很大程度上仍不清楚。在此，我们基于基因表达综合数据库（GEO）的转录组序列，报告了蒙古人肝细胞癌和白种人HCC中的差异表达基因（DEG）及其交集DEG，以及蒙古人和白种人肝细胞癌患者相应的信号通路。我们在蒙古人HCC中得到908个上调基因和1946个下调基因，在白种人HCC中得到1244个上调基因和1912个下调基因，在蒙古人和白种人中得到254个共同上调基因和1035个共同下调基因。基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析结果表明，蒙古人HCC中表达水平改变的大多数基因参与涉及各种物质代谢重编程的生物学过程，约占所有生物学过程的三分之一。特别是，与白种人HCC相比，多种氨基酸生物合成和代谢过程在蒙古人HCC中似乎具有特异性。它们共有的生物学过程包括大多数免疫细胞参与的过程和与细胞周期相关的生物学过程。此外，我们还发现基因UPP2、PCK1、GLYAT、GNMT、ADH1B和HPD编码关键代谢酶，其表达水平在蒙古人HCC中上调或下调超过5倍，并且与蒙古人HCC的生存率显著相关（p值<0.01），更重要的是，这些分子是一些代谢抗肿瘤药物的潜在靶点。本研究不仅弥补了以往肝癌研究中更多关注其共性而忽视不同种族和地区肝癌特异性的不足。更重要的是，本研究的目的是识别具有潜在独特肿瘤生物学特性的强大分子亚类和信息。并且本研究可能对肝细胞癌的致病因素和分子机制研究以及蒙古人HCC的精准治疗具有重要意义。
