Alterations in glycolytic/cholesterogenic gene expression in hepatocellular carcinoma
Alterations in glycolytic/cholesterogenic gene expression in hepatocellular carcinoma
复制标题
肝细胞癌中糖酵解/胆固醇生成基因表达的变化
DOI：
10.18632/aging.103254
复制
发表时间：
2020-06-15
期刊：
影响因子：
5.2
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
--
作者：
Jiang, Jianwen;Zheng, Qiuxian;Zheng, Shusen
代谢重编程是肿瘤的一个标志，包括肝细胞癌（HCC）。我们使用来自癌症基因组图谱和国际癌症基因组联盟的数据来评估HCC中糖酵解和胆固醇生成基因的改变，并确定它们与HCC患者临床特征的关系。基于这些数据库中的基因表达谱，我们建立了四种HCC亚型：胆固醇生成型、糖酵解型、混合型和静止型。胆固醇生成亚组预后较糖酵解组差。糖酵解组肿瘤对化疗更敏感。我们还探讨了这些代谢亚型与先前建立的HCC亚群之间的关系。在Hoshida HCC分类中，糖酵解基因表达与预后较差的基因表达密切相关。全基因组分析表明，HCC中TP53和MYC的异常扩增与合成代谢胆固醇代谢异常有关。线粒体丙酮酸载体1和2的mRNA水平在HCC代谢亚型中存在差异。在生物信息学分析中，我们确定了不同癌症类型之间肿瘤代谢的基因组特征。这些发现表明代谢亚型可能是HCC患者有价值的预后指标。
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.