Screening Of BaP Induced Hcc Related Genes Based On GEO Database And Its Impact On The Occurrence And Prognosis Of HCC

Objective: To explore the induction mechanism of benzopyrene(BaP)-mediated hepatocellular carcinoma(HCC)using GEO dataset analysis,to cluster genes with similar expression patterns combined with weighted gene co-expression network analysis,and to analyze the association between modules and specific traits or phenotypes,and to identify potential biomarkers useful in HCC diagnosis,novel drug treatment and development.Research Methods: We screened the primary human hepatocytes dataset GSE127791 treated with BaP as the keyword "BaP,liver"."P < 0.05,|log2FC| > 1" was used as a condition for GEO2 R analysis of valid DEGs in the GSE127791 dataset.Take String to explore protein-protein interactions of DEGs and visualize protein interaction networks using the Cytoscape 3.6.1 tool.Subsequently,the Cytoscape software program MCODE was used to screen the more important parts of the PPI network and use DAVID for biological analysis.Then,based on the weighted gene co-expression network analysis algorithm,Download the patient’s RNA sequencing data and clinical information from UCSC Xena website at UC Santa Cruz,to construct gene co-expression modules,and study the relationship between key modules and clinical phenotypes,and weighted gene co-expression network analysis(WGCNA)determined the gene modules related to the clinical characteristics of HCC patients.Establish key genes related to hepatocellular carcinoma(HCC)according to the absolute value of the correlation between genes and phenotypic traits of genes in the module,the correlation between the characteristic genes and gene expression profiles of the module,and the connectivity within the module.Mutation landscape analysis yields gene mutation status,and the GEPIA database is used to determine the expression level of meaningful mutant gene genes and differences between hepatocellular carcinoma and adjacent cancer samples at the gene level,followed by survival analysis by key gene.Results: According to cluster analysis and protein co-expression network,we identified a total of 1096 up-regulated genes and 181 down-regulated genes,and screened out key gene cyclin-dependent kinase 1(CDK1)and gene topoisomerase IIα(TOP2A)、Mitotic checkpoint serine(BUB1).GO analysis showed that DEGs were regulated in multicellular biological processes、anatomical structure development、multicellular biological processes 、 multicellular biological development and developmental processes.The presence of ECM-related effects is shown in KEGG,where interactions between ECM and cell surface receptors regulate cell behavior and play an important role in cell-to-cell communication,cell proliferation,adhesion,and migration.Weighted gene co-expression showed that the characteristic gene of turquoise was positively correlated with HCC(r = 0.68,P < 0.01),and the clinical data toxicity test showed that 8 genes such as ASPM and BUB1 were associated with the adverse prognosis of hepatocellular carcinoma,and the mutation landscape is used to visualize mutations in 8 central genes.IQGAP3 has the highest mutation rate(14%),with enlarged mutations being the most common.PBK has the highest rate of deep deletion mutations(6%),the most common mutation is deep deletion,and survival analysis shows that increased expression of CDK1 and BUB1 indicates a poor prognosis for HCC.Conclusion: The increase in CDK1 and BUB1 expression after hepatocytes exposed to BaP may be related to BaP-induced hepatocyte damage and carcinogenesis,in addition,the increased expression of CDK1 and BUB1 in HCC initiation and progression indicates that HCC has a poor prognosis.