Abstract:

Objective To identify the key genes associated with the early diagnosis and poor prognosis of hepatitis B virus-associated hepatocellular carcinoma （HBV-HCC） by using the bioinformatics methods， and to elucidate the underlying molecular mechanism of occurence and development of HBV-HCC. Methods Gene Expression Omnibus （GEO） Database was used to retrieval “hepatitis B induced HCC”； the Gene Dataset GSE121248 was downloaded， the differentially expressed genes （DEGs） were screened by the “limma” Data Package in R Software， and the DEGs were enriched by using the “clusterProfiler” Data Package for Gene Ontology （GO） functional analysis and the Kyoto Genes and Genome Encyclopedia （KEGG） signaling pathway enrichment analysis； STRING Database and Cytoscape Software were used to establish the protein-protein interaction（PPI） network and the key genes were screened out.Gene Expression Profiling Interactive Analysis（GEPIA）， Kaplan Meier-Plotter，and Human Protein Atlas（HPA）Databases were used to verify the key genes and the expression levels of proteins；the infiltration of the immune cells was analyzed based on the “CIBERSORT” Data Package. Results A total of 574 DEGs were identified，including 173 up-regulated genes and 401 down-regulated genes. The GO functional enrichment analysis results showed that DEGs were mainly enriched in the biological processes such as small molecule metabolism， signal transduction， immune response， inflammatory response，and so on； the KEGG signaling pathway enrichment analysis results showed that the DEGs were mainly enriched in retinol metabolism， cytochrome P450 metabolic pathway of exogenous drugs， and chemical carcinogenesis，and so on. The PPI network results showed that cell division cycle 20（CDC20），cyclin dependent kinase 1（CDK1）， cyclin A2（CCNA2）， pindle checkpoint protein（BUB1B）， topoisomerase Ⅱ α（TOP2A）， discs large homolog associated related protein 5（DLGAP5）， abnormal spindle-like microcephaly associated protein（ASPM）， centrosomal protein 55（CEP55）， kinesin superfamily 11（KIF11），and kinesin superfamily 20A（KIF20A） were the key genes. The GEPIA Database analysis results showed that these above 10 key genes were highly expressed in the HCC patients. The Kaplan Meier survival curve showed that the overall survivals of the HCC patients with high expression of key genes were shorter than those of the HCC patients with low expression of key genes. Conclusion The genes related to cell cycle and viral oncogenesis （CDC20， CDK1， CCNA2， and BUB1B） are closely associated with the occurence and development and poor prognosis of the HBV-HCC patients， which may become the diagnostic markers and new targets for the treatment.

Key words: Hepatocellular carcinoma, Hepatitis B virus, Bioinformatics, Immune infiltration, Prognosis