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The Expression Of CGAS/STING Pathway In Cancer Tissues And Its Correlation With Immune Cell Infiltration

Posted on:2020-06-08Degree:MasterType:Thesis
Country:ChinaCandidate:S Y TianFull Text:PDF
GTID:2404330590492858Subject:Pathology and pathophysiology
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?Objectives?: 1.To study the expression of four key molecules(MB21D1 ? TMEM173 ? TANK-binding kinase 1(TBK1)and IFN-regulated factor 3(IRF3))in cGAS/STING signaling pathway and their methylation level in cancer.2.To explore whether cGAS/STING signaling is associated with immune cell infiltration in some tumor types.3.To investigate whether high levels of cGAS/STING can predict the prognosis of patients with certain malignancies and provide evidence for the clinical application of anti-cancer immunity.?Methods?:Cancer mRNA RNA-Seq-HTSeq fragment per megabase exon model per million mapping reads,methylation level data,and correlations between methylation and expression of different target genes were obtained from TCGA,MethHC and cBioPortal databases.The correlation between immune cell infiltration and key molecule expression in cGAS/STING signal transduction and the correlation between cGAS/STING pathway and clinical CTLA-4 block efficacy were analyzed.The effect of MB21D1,TMEM173,TBK and IRF3 mRNA expressions on prognosis were evaluated by interactive analysis using gene expression profile analysis.?Results?: 1.cGAS/STING signales were universally elevated based on the expression of MB21D1,TMEM173,TBK1 and IRF3 in Pan-cancer.2.The promoter methylation levels of MB21D1,TMEM173,TBK1 and IRF3 were various in different types of malignant cancers.3.A high somatic mutation rate in the MB21D1,TMEM173,TBK1 and IRF3 genes is present in Pan-cancer.4.The expression of MB21D1,TMEM173,TBK1 or IRF3 genes in cancer microenvironment was associated with immune cell infiltration.5.The expression level of MB21D1,TMEM173,TBK1 and IRF3 genes were associated with the prognosis of cancer patients.?Conclusions?:The cGAS/STING signales were highly expressed in pan-cancer tissues.The highly upregulated cGAS/STING signales is negatively correlated with the infiltration of immune cells in some cancer types.
Keywords/Search Tags:cGMP-AMP(cGAMP) synthase(cGAS), Stimulator of interferon genes(STING), TBK1, IRF3
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