Frontiers in Pharmacology (Oct 2022)
A comprehensive analysis of the prognostic value and immune infiltration of low expression DBT in clear cell renal cell carcinoma
Abstract
Background: Although DBT is strongly associated with human tumorigenesis and progression through a variety of pathways, the role of DBT in clear cell renal cell carcinoma (ccRCC) has not been well established.Materials and methods: The Cancer Genome Atlas (TCGA)-Kidney renal clear cell carcinoma (KIRC) databset provides RNA sequencing data and clinicopathological information on ccRCC. The Gene Expression Omnibus (GEO) database was used to validate the DBT expression levels, and qPCR was used to examine the DBT expression in renal cancer cell lines and ccRCC tissue samples from our centre. In parallel, DBT protein expression was explored in the Human Protein Atlas (HPA) database, and western blotting and immunohistochemistry of renal cancer cell lines and ccRCC tissues validated the results. Additionally, the diagnostic and prognostic value of DBT was comprehensively evaluated by receiver operating characteristic (ROC) curves, univariate and multivariate Cox regression analyses, and Kaplan‒Meier survival analysis. The protein‒protein interaction (PPI) network based on the STRING website, Gene Ontology (GO) analysis, Kyoto Gene and Genome Encyclopedia (KEGG) analysis and gene set enrichment analysis (GSEA) further provided a landscape of the molecular mechanisms of DBT in ccRCC. Finally, the TIMER 2.0, GEPIA and TISIDB websites were used to understand the relationship between DBT and immune characteristics.Results: The mRNA expression and protein expression of DBT were significantly downregulated in ccRCC tissues relative to normal tissues, which was associated with poor clinical outcomes. DBT has an encouraging discriminatory power for ccRCC and is an independent prognostic factor for ccRCC patients. Mechanistically, DBT is mainly involved in the regulation of immune-related signalling pathways in ccRCC; it is associated with a variety of immune infiltrating cells and immune checkpoints.Conclusion: DBT is a tumour suppressor gene in ccRCC and could be used as a new biomarker for diagnostic and prognostic purposes, and it is associated with immune infiltration in ccRCC.
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