Screening Of Susceptible Biological Targets For Hepatocellular Carcinoma Based On Bioinformatics Analysis

Objective:Excavate the data of hepatocellular carcinoma gene chip,screen out the susceptible biological target molecules related to hepatocellular carcinoma,initially explore the biological function enrichment pathway in the occurrence and development of hepatocellular carcinoma,construct the disease module of hepatocellular carcinoma and conduct functional analysis,To provide evidence for the etiological research and early diagnosis of patients with hepatocellular carcinoma.Methods:?1?The hepatocellular oncogene chip data GSE14520 was retrieved from the GEO database in NCBI from the platform GPL3921.The data set is a whole-genome RNA expression chip of human origin.A total of 225 hepatocellular carcinoma tissue specimens and 220 normal adjacent tissue specimens were selected for subsequent research.?2?Use the GEO2R online analysis platform to standardize the gene chip data,and use|log₂FC|>1,P.adjust<0.05 as the standard to screen out differentially expressed genes for hepatocellular carcinoma.?3?Use the DAVID online analysis tool to screen the top 250 Hepatocellular carcinoma differentially expressed genes for GO functional enrichment analysis and KEGG pathway enrichment analysis.?4?Use the String online analysis platform to build a protein-protein interaction network of differentially expressed genes and visual analysis was performed using Cytoscape 3.6.1 software.Use the MCODE application plug-in to perform modular analysis of the protein-protein interaction network,and use the DAVID online analysis platform to enrich the biological functional pathways of the differential genes in each module to obtain the biological functions represented by each disease module.?5?Use CytoHubba screens the core genes of the protein interaction network and sorts them according to the degree of connectivity to select the core genes.?6?Through the preliminary bioinformatics analysis and literature database search,meta-analysis of the relationship between the obtained hepatocellular carcinoma susceptibility gene and the occurrence and development of the disease,comprehensive analysis of previous research,to achieve the purpose of supplementation and verification of bioinformatics research,with a view to get a more comprehensive analysis of the relationship between susceptibility genes and the occurrence and development of hepatocellular carcinoma.Results:?1?The GSE14520 data set was analyzed,and the top 250hepatocellular carcinoma differentially expressed genes were ranked by GEO2R screening,of which 122 genes were up-regulated and 128 genes were down-regulated.?2?GO functional biological processes analysis showed that the differentially expressed genes of hepatocellular carcinoma were in the process of mitotic cell cycle,cell cycle process,cell division,mitotic cell cycle phase transition,cell response to zinc ions,cell cycle regulation,nuclear division,and chromosomal tissue pathways;KEGG pathway enrichment analysis shows that hepatocellular carcinoma differentially expressed genes are involved in mineral absorption,cell cycle,DNA replication,retinol metabolism,metabolic pathways,drug metabolism-other enzymes,caffeine metabolism,oocyte meiosis Drug Metabolism-Cytochrome P450,Cytochrome P450 plays a regulatory role in biological pathways such as metabolic pathways of other organisms.?3?Construct PPI network and get a total of 195 genes,CytoHubba screened the core genes of the PPI network,suggesting that CDK1?Degree Score=63?,RFC4?Degree Score=59?,CDC20?Degree Score=58?and CCNB1?Degree Score=57?may play an important regulatory role in the occurrence of hepatocellular carcinoma.?4?Analysis of the network module of the MCODE application of Cytoscape3.6.1 software shows that there are four major disease modules,of which the disease module A with the highest MCODE score?MCODE Score=41.143?is mainly related to cell cycle,DNA replication,oocyte meiosis,progesterone-mediated maturation of oocytes,p53 signaling pathway and human T lymphocytic leukemia virus type I infection pathway are related.?5?Through the meta-analysis,the CYP2E1 genotype frequency distribution in the Chinese population was not statistically associated with an increased risk of developing hepatocellular carcinoma,Combined OR=0.67?95%CI:0.39,1.14?,Z=1.48,P=0.14;the highexpression of PTTG1 in the Chinese population was associated with an increased risk of developing hepatocellular carcinoma,and the association was statistically significant,Combined OR=7.94?95%CI:1.22,51.85?,Z=2.16,P=0.03.Conclusion:?1?The results showed that the generation of hepatocellular carcinoma may be related to abnormal processes of the cell cycle and mitosis,among which genes such as CDK1,RFC4,CDC20,and CCNB1 may play a key role in the progression of tumor in hepatocellular carcinoma,which can be used as a potential susceptible biological target for subsequent research of hepatocellular carcinoma.?2?The high expression of PTTG1 gene may be a risk factor for the development of hepatocellular carcinoma.