Abstract
BackgroundAutophagy related protein 5 (ATG5) is an important autophagosome formation related protein, and its involvement in the biological process of autophagy has been shown to correlate with tumor metabolic patterns and the formation of tumor heterogeneity. However, the role of ATG5 in tumor metabolism and tumor immunity remains unclear.MethodIn order to explore this problem, this study was designed to reveal the role of ATG5 in tumor metabolism and tumor immunity through pan-cancer analysis of multi-database. GTEx database, CCLE database, and TCGA database were used to describe the expression, prognosis, immune microenvironment, immune new antigen, immune checkpoint, TMB, and microsatellite instability of ATG5 in 33 types of tumors. A series of bioinformatics tools and methods were used for quantitative analysis and panoramic description, such as to Estimate, Scanneo and GSEA.ResultThe differential analysis results of multiple databases showed that ATG5 was ubiquitously highly expressed in pan-cancer, especially in solid tumors. Survival analysis revealed that ATG5 was universally associated with the prognosis of pan-cancer, and high ATG5 expression was significantly associated with poor patient prognosis in most cases. Further, the expression level of ATG5 was confirmed to be associated with tumor immune infiltration and tumor microenvironment, especially in BRCA, KIRC, and LIHC. In addition to this, ATG5 expression was confirmed to correlate with these clinically significant phenotypes, in conjunction with immune neoantigens and immune checkpoint gene expression profiles in pan-cancer. In addition to TMB and microsatellite instability in pan-cancer, we confirmed that ATG5 expression affects the expression of DNA repair genes and methyltransferases in pan-cancer, and found through gene set enrichment analysis that ATG5 is involved in the regulation of numerous signaling pathways involved in cancer metabolism and cancer immunity.ConclusionsATG5 participated in the formation of autophagosomal membrane important molecule LC3-II outside, and played an important role in tumor metabolism and tumor immunity. The comprehensive pan-cancer analysis not only revealed the potential of ATG5 in tumor-targeted therapy but also suggested ATG5 as a promising tumor predictive biomarker in most solid tumors.
Highlights
Autophagy related protein 5 (ATG5) is an important autophagosome formation related protein that functions as an E1-like activating enzyme in eukaryotic cells [1, 2]
Pyrimidine metabolism, small cell lung cancer, renal cell carcinoma, chronic myeloid leukemia, and pathways in cancer were described as the most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, glycolysis, PI3K-Akt-mTOR signaling, mTORC1 signaling, DNA repair, Myc targets, adipogenesis, TGF-beta signaling pathway, IL2STAT5 signaling pathway And oxidative phosphorylation and other biological processes were described as hallmark signaling pathways with the greatest enrichment, these results indicate that ATG5 is widely involved in the regulation of signaling pathways involved in tumor metabolism and tumor immunity
This metabolic pattern is characterized by enhanced uptake of glucose and amino acids by tumor cells, opportunistic nutrient utilization patterns, differential glycolysis/TCA cycle pathways, increased demand for nitrogen elements, a metabolite driven pattern of gene regulation, and interaction with metabolites in the tumor microenvironment, features that are widely used for tumor-specific targeted drug development [17]
Summary
Autophagy related protein 5 (ATG5) is an important autophagosome formation related protein that functions as an E1-like activating enzyme in eukaryotic cells [1, 2]. Antagonism of autophagy with inflammation decreased the degree of chronic inflammatory infiltration and repressed the inflammatory cancer transformation process. These biological processes, which influence cell fate decisions, conspire at distinct effects of tumor stromal cells and versus tumor immune cells to program tumor metabolic patterns and shape the tumor immune landscape [10, 11]. Autophagy related protein 5 (ATG5) is an important autophagosome formation related protein, and its involvement in the biological process of autophagy has been shown to correlate with tumor metabolic patterns and the formation of tumor heterogeneity. The role of ATG5 in tumor metabolism and tumor immunity remains unclear
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