Screening Of Pyroptosis Related Genes By An Integrated WGCNA-META-Analysis

Pyroptosis is a type of programmed cell death characterized by the lytic death of cells.It is characterized by the release of pro-inflammatory cytokines and the resulting inflammatory response.Gasdermin protein family are the effector molecules in pyroptosis,which can be activated by some members of the caspase family(apoptosis execution proteins)to trigger pyroptosis.Therefore,these pyroptosis pathways occur after the initiation of the apoptosis program,but in this process,the mechanism that affects the final apoptosis or pyroptosis of cells is not completely clear.Therefore,this study used bioinformatics to explore the key regulatory genes in the process of pyroptosis and explored the impact of key genes on the survival of cancer patients.We screened the pyroptosis-related human transcriptome data sets from three databases,NCBI,EBI,and DDBJ,and extracted the data of the pyroptosis group and the control group.By using WGCNA-Meta DE analysis,we screened pyroptosis-related gene modules and differentially expressed genes,and then intersect them with apoptosis-related regulatory genes,and perform GO,KEGG and response group pathway enrichment analysis;In addition,we screened out key modules and differentially expressed genes,and finally the hub gene of the two analysis methods are intersected.Afterwards,we used TPH1 cells to establish a pyroptosis model,and used q PCR experiments to detect the expression levels of the predicted genes.The research results show that the apoptosis-related pyroptotic genes screened by WGCNA and Mate DE are enriched in biological processes such as cell signal transduction,cell proliferation,cell cycle regulation,and protein synthesis.Common key genes include GTPBP4,NIFK,CHD4,AURKA,RRP1 B,CKAP5,RPL15,TOP2 A,etc.were screened,and their correlation coefficient with pyroptosis traits is-0.39.After LPS and Nigericin treatment of TPH1 cells,GTPBP4,NIFK,CHD4,m RNA expression levels were downregulated,which showed that these genes have an important regulatory role in the process of cell pyroptosis.When the expression levels of GTPBP4,NIFK,CHD4,and AURKA were downregulated,the survival time of patients with various tumors was significantly prolonged.