BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cel...BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cells,and the rapidly proliferating tumour cells are powered by aerobic glycolysis.Lipid metabolism reprogramming enables tumour cells to meet their needs for highly proliferative growth and is an important driving force for the development of hepatocellular carcinoma(HCC).AIM To explore the influence of different metabolic subtypes of HCC and analyse their significance in guiding prognosis and treatment based on the molecular mechanism of glycolysis and fatty acid oxidation(FAO).METHODS By downloading related data from public databases including the Cancer Genome Atlas(TCGA),the Molecular Signatures Database,and International Cancer Genome Consortium,we utilised unsupervised consensus clustering to divide TCGA Liver Hepatocellular Carcinoma samples into four metabolic subgroups and compared single nucleotide polymorphism,copy number variation,tumour microenvironment,and Genomics of Drug Sensitivity in Cancer and Tumour Immune Dysfunction and Exclusion between different metabolites.The differences and causes of survival and the clinical characteristics between them were analysed,and a prognostic model was established based on glycolysis and FAO genes.Combined with the clinical features,a Norman diagram was created to compare the pros and cons of each model.RESULTS In the four metabolic subgroups,with the increase in glycolytic expression,the median survival of patients showed the worst results,while FAO showed the best.When comparing the follow-up analysis of each group,we considered that the differences between them might be related to reactive oxygen species,somatic copy number variation of key genes,and immune microenvironment.It was also found that the FAO group and the low-risk group had better efficacy and response to immune checkpoint blockade treatment and anti-tumour drugs.CONCLUSION There are obvious differences in genes,chromosomes,and clinical characteristics between metabolic subgroups.The establishment of a prognostic model could predict patient prognosis and guide clinical treatment.展开更多
基金Supported by the Project of National Natural Science Foundation of China,No.81802365 and 81802385the Special Project of Clinical Key Diseases Treatment Technology in Suzhou,No.LCZX2019003+2 种基金the City-Level Scientific Research Projects in Jiangsu Province,No.SLT201907Major Projects of Provincial Universities in Jiangsu Province,No.19KJA170002Soochow University Horizontal Research Project,No.H190168.
文摘BACKGROUND Metabolic reprogramming is a feature of tumour cells and is essential to support their rapid proliferation.The glycolytic activity of liver cancer cells is significantly higher than that of normal liver cells,and the rapidly proliferating tumour cells are powered by aerobic glycolysis.Lipid metabolism reprogramming enables tumour cells to meet their needs for highly proliferative growth and is an important driving force for the development of hepatocellular carcinoma(HCC).AIM To explore the influence of different metabolic subtypes of HCC and analyse their significance in guiding prognosis and treatment based on the molecular mechanism of glycolysis and fatty acid oxidation(FAO).METHODS By downloading related data from public databases including the Cancer Genome Atlas(TCGA),the Molecular Signatures Database,and International Cancer Genome Consortium,we utilised unsupervised consensus clustering to divide TCGA Liver Hepatocellular Carcinoma samples into four metabolic subgroups and compared single nucleotide polymorphism,copy number variation,tumour microenvironment,and Genomics of Drug Sensitivity in Cancer and Tumour Immune Dysfunction and Exclusion between different metabolites.The differences and causes of survival and the clinical characteristics between them were analysed,and a prognostic model was established based on glycolysis and FAO genes.Combined with the clinical features,a Norman diagram was created to compare the pros and cons of each model.RESULTS In the four metabolic subgroups,with the increase in glycolytic expression,the median survival of patients showed the worst results,while FAO showed the best.When comparing the follow-up analysis of each group,we considered that the differences between them might be related to reactive oxygen species,somatic copy number variation of key genes,and immune microenvironment.It was also found that the FAO group and the low-risk group had better efficacy and response to immune checkpoint blockade treatment and anti-tumour drugs.CONCLUSION There are obvious differences in genes,chromosomes,and clinical characteristics between metabolic subgroups.The establishment of a prognostic model could predict patient prognosis and guide clinical treatment.
