Study On The Relationship Between GATOR1 And Hepatocellular Carcinom

Meta Analysis of the relationship between DEPDC5 Gene Polymorphism and Hepatocellular carcinoma susceptibilityObjective: DEPDC5 is one of the subunits of GATOR1 complex.In recent years,there are different conclusions on the relationship between DEPDC5 gene polymorphism and hepatocellular carcinoma susceptibility.Therefore,we systematically reviewed the association between rs1012068 and rs5998152 polymorphisms of DEPDC5 gene and HCC susceptibility,and then discussed the biological function of these two sites.Methods: 1.Based on the method of Meta analysis,the relationship between rs1012068 and rs5998152 single nucleotide polymorphisms of DEPDC5 gene and susceptibility to HCC was systematically evaluated.As of October 31,2022,NCBI Pub Med,Embase,Scopus,Web of Science and China knowledge Network(CNKI)were used to search the relationship between rs1012068,rs5998152 and susceptibility to HCC.The OR values and95%CI of the five genetic models were calculated,and the Rev Man5.3software was used for Meta analysis.2.DEPDC5 rs1012068 and rs5998152 were analyzed by 3d SNP online analysis software to explore the possible changes in biological function caused by mutation.Results: 1.Meta analysis included 12 articles,11 articles about rs1012068 SNP locus,2609 patients with hepatocellular carcinoma and 8171 controls,and 3 articles about rs5998152 SNP locus included 411 patients with hepatocellular carcinoma and 1448 controls.The results of Meta analysis showed that among the five genetic models of rs1012068 SNP locus,allele pattern(G vs T: P=0.02),dominant pattern(GG+TG vs TT: P=0.01)and heterozygote pattern(TG vs.TT: P=0.009)were significantly different between the case group and the control group.In homozygous mode(GG vs TT: P=0.05)and recessive mode(GG vs TG+TT: P=0.08),there was no correlation between rs1012068 gene polymorphism and susceptibility to liver cancer.Among the five genetic models of rs5998152 SNP locus,allele model(C vs.T: P=0.03),dominant model(CC+TC vs TT: P <0.001)and heterozygous model(TC vs TT: P <0.001)were significantly different between case group and control group(P<0.001).Recessive model(CC vs TC+TT: P=0.31)and homozygous model(CC vs TT: P=0.09).There was no correlation between rs5998152 gene polymorphism and susceptibility to liver cancer.2.3d SNP analysis showed that the mutations of rs1012068 and rs5998152 affected the relationship between the genes associated with them at the chromosome level.Conclusions: 1.Rs1012068 SNP locus in allele model,dominant gene model and heterozygote pattern,there is a correlation between rs1012068 SNP locus and susceptibility to liver cancer,which is a promoting genetic factor leading to tumorigenesis.The allele pattern,dominance pattern and heterozygote pattern of rs5998152 SNP locus can increase the risk of liver cancer,but no correlation was found in other patterns.2.The variation of rs1012068 and rs5998152 may affect the biological function of the genes that interact with them in the chromatin ring.The Prognostic Value of NPRL2 and NPRL3 in Hepatocellular Carcinoma and their Relationship with Immune InfiltrationObjective: To explore the expression and biological function of NPRL2 and NPRL3 in human hepatocellular carcinoma and their relationship with prognosis and immune infiltration,and to construct a prognostic model.Methods: the expression differences of NPRL2 and NPRL3 in LIHC and normal liver tissues were analyzed by multiple gene expression databases.The relationship between e IF4E3 protein expression and different clinicopathological features of LIHC was analyzed by UALCAN database and HPA database.Survival analysis was performed by GSCA,UALCAN,GEPIA2 database and Kaplan-Meier Plotter.The co-expression genes of e IF4E3 were explored by Linked Omics and GEPIA2 databases,and the genes obtained from Wayne diagram were analyzed by GO and KEGG.TISIDB database,Sanger Box database,TIDE database and TIMER database were used to analyze the relationship between e IF4E3 and immune infiltration in tumor microenvironment,and Kaplan-Meier Plotter was used to map the prognosis under different immune conditions.Finally,download the transcriptional and clinical information of TCGA-LIHC and GSE10141 data sets,integrate the data,and use R software to build prognostic models related to NPRL2 and NPRL3 coexpression genes.Results: The expression levels of NPRL2 and NPRL3 in LIHC were significantly higher than those in matched normal liver tissues(P<0.05).In the four databases,the overexpression of e IF4E3 was significantly correlated with poor survival(P<0.05).Functional enrichment analysis showed that NPRL2 coexpression genes were mainly involved in mitochondrial gene expression and peptide biosynthesis,enriched in ribosome,proteasome,RNA degradation and RNA transport pathways,and NPRL3 enriched in m TOR signaling pathway,ribonucleic acid transport and autophagy pathways.The expression of NPRL2 affects the infiltration level of immune cells in LIHC,which is positively correlated with the gene of immune checkpoint,and the evidence of the relationship between NPRL3 and immune microenvironment is insufficient.The prognostic prediction model based on NPRL2 coexpression gene can better predict the prognosis of HCC patients.The predictive ability and accuracy of the prognostic model based on NPRL3 coexpression gene are not high.These results suggest that NPRL2 and NPRL3 have prognostic value in HCC.Part of the reason for affecting the prognosis may be that it affects the infiltration level of HCC immune infiltrating cells,which lays a foundation for further study of the immunomodulatory role of NPRL2 and NPRL3 in hepatocellular carcinoma.Conclusion: NPRL2 and NPRL3 may be potential oncogenes in HCC,which may affect the prognosis by inducing immune infiltration of hepatocellular carcinoma,and are expected to become a new prognostic biomarker and therapeutic target of HCC.