| Objective: To study cancer-related pathways,explore key prognostic genes of hepatocellular carcinoma(HCC)patients,analyze the prognostic pathways of HCC,find biomarkers that predict the prognosis of HCC patients,and explore potential therapeutic targets of HCC.Methods: From high-throughput gene expression database(gene expression omnibus,GEO)(https://www.ncbi.nlm.nih.gov/geo/)download HCC in two related microarray expression data set.The gene expression matrices of HCC tissue samples and non-tumor liver tissue samples were extracted respectively,and the Limma package in R language was used to analyze the differences of expressed genes in HCC tissue samples and non-tumor liver tissue samples,and the screening criteria were(P< 0.05 and |log2FC| > 1).The different genes obtained from the two data sets were intersected by Venn diagram.Using the Enrichr database,KEGG(The Kyoto Encyclopedia of Genes and Genomes)correlation pathway analysis and GO(Gene Ontology)enrichment analysis were conducted for the intersected differential genes.Furthermore,the protein-protein interaction network mapping analysis of the differential genes was carried out using the online tool STRING.Only the interacting differential proteins were retained,and further analysis was made through the MCODE(molecular complex detection)plug-in in Cytoscape software to screen the modules with the highest comprehensive score,and the genes from them were extracted as hub genes.The differences in hub genes expression,overall survival rate,disease-free survival rate,and tumor stage were analyzed in GEPIA database,and the differences in hub genes expression,HCC stage,HCC grade,overall survival rate,TP53 mutation,and lymph node metastasis were analyzed in UALCAN database,genes differentially expressed between HCC tissue samples and non-tumor liver tissue samples that significantly affected the prognosis of HCC patients were screened(P <0.05)as key genes.To select biomarkers that might have prognostic significance in HCC patients,further KEGG pathway analysis and GO analysis were performed using the Enrichr database.Results:(1)A total of 174 differentially expressed genes were screened between HCC tissue samples and non-tumor liver tissue samples.(2)KEGG analysis and GO analysis showed that 174 differentially expressed genes were concentrated in glycolysis,arachidonic acid metabolism,PPAR(peroxisome proliferating-activated receptor),amino acid metabolism and other signaling pathways,amino acid metabolism and other signaling pathways,enriched in biological processes such as complement activation,cytochrome P450,amino acid metabolism,arachidonic acid metabolism,elongation of the spindle,etc,enriched in membrane attack complex,spindle centrosomes,spindle poles,microtubules and other cellular components,enriched in molecular functions such as arachidonic acid cycoxidase activity,histone serine kinase activity,etc.(3)Spring and Cytoscape were used to screen out 21 hub genes from 174 differential genes,and GEPIA and UALCAN were used to screen out17 key genes with differential expression in HCC tissue samples and non-tumor liver tissue samples and affecting prognosis of HCC patients(P < 0.05).(4)KEGG analysis and GO analysis showed that 17 key genes were concentrated in cell cycle,oocyte maturation,Fanconi anemia,and human T-cell leukemia virus infection signaling pathway,enrichment involves the assembly of the middle region of spindle,the attachment of spindle microtubules and centromere,and the concentration of chromosomes,enriched in spindles,chromosome concentration and other cellular components,enriched in molecular energy such as histone serine kinase activity,histone kinase activity and microtubule motor movement.Conclusion:(1)174 differentially expressed HCC genes were screened out,which were mainly enriched in glycolysis,arachidonic acid metabolism,amino acid metabolism,fatty acid metabolism,PPAR and other pathways,and were involved in the occurrence and development of HCC.(2)Seventeen key genes related to the prognosis of HCC patients were screened,which could be used as prognostic markers in HCC patients.(3)The 17 key genes are mainly enriched in the cell cycle,oocyte maturation,Fanconi anemia and other pathways.Cell cycle plays a role in the occurrence and development of hepatocellular carcinoma.Cell cycle is closely related to glycolysis and lipid metabolism,which influence each other in the occurrence and development of HCC and affect the prognosis of HCC patients.(4)All the 17 key genes were up-regulated genes in HCC tissues,and the low expression levels of key genes were negatively correlated with TP53 mutation in HCC tissues. |
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