Identification Of Aerobic Glycolysis-Related Prognosis Signature For Predicting Overall Survival Of Patients With Hepatocellular Carcinoma

Background:Aerobic glycolysis,also known as the "Warburg effect",is the process by which glucose is oxidized to pyruvate and then lactic acid is produced under aerobic conditions.Aerobic glycolysis is characterized by increased glucose uptake,consumption,and lactic acid release.Over the past decade,aerobic glycolysis has played a carcinogenic role in cancer,which is one of the evidences of tumor metabolic changes,resulting in tumor acidosis by promoting tumor biomass synthesis(such as nucleotides,lipids,and non-essential amino acids),high-speed ATP production,lactic acid accumulation,and so on.Aerobic glycolysis is involved in tumor proliferation,growth,metastasis,invasion,resistance to certain antitumor therapies,and impairs antitumor immunity.The target of tumor glycolysis was used to provide prospective therapeutic strategies for tumor therapy.However,the molecular mechanism of aerobic glycolysis in Hepatocellularcarcinoma(HCC)remains unclear.Methods:mRNA expression profiles and clinical information were obtained from Cancer Genome Atlas(TCGA),International Cancer Genome Consortium(ICGC)and Integrated Gene Expression(GEO)databases.Aerobic glycolysis related genes(ARGs)were obtained from molecular signature database(MSigDB).DE-ARGs between HCC and non-tumor samples were identified,and prognostic features and effective prediction models were constructed for HCC.We also delved into the biological function,immune infiltration immune checkpoint related gene expression,and response to immunotherapy and targeted therapy in the risk-associated group.Results:We comprehensively analyzed the characteristics of ARGs and their role in the prognosis of HCC.A total of 1752 DeGs(1505 up-regulated and 247 down-regulated)were detected between HCC tissues and adjacent tissues.A total of 23 HCC DE-ARGs were screened,among which 13 DE-ARGs were associated with OS in HCC patients.We then constructed LASSO regression to select genetic markers associated with prognosis(KIF20A,CENPA,HMMR,G6PD,EFNA3,and ADH4).KIF20A acts as an oncogene in HCC to promote the growth and survival of HCC cells,and is associated with poor HCC survival and relapse-free survival.CENPA is an epigenetic marker involved in a variety of cancers as a transcriptional regulator.In addition,HMMR,G6PD,EFNA3 and ADH4 were significantly overexpressed in cancer.Compared with the low-risk group,the high-risk group of HCC patients had poor OS.The high-risk group was involved in biological processes associated with copper ions.In addition,the high risk score was associated with activated immun cells and sensitivity to better response to immunotherapy,as well as adverse reactions to chemotherapy.Conclusions:We identified DE-ARGs between HCC and non-tumor samples,and constructed prognostic features and effective prediction models for HCC.We also delved into the biological function,immune infiltration immune checkpoint related gene expression,and response to immunotherapy and targeted therapy in the risk-associated group.Our results suggest a key and dominant role of aerobic glycolysis in HCC,providing new insights into diagnostic and therapeutic strategies for HCC.