ALAD Expression and Prognostic Value in Solid Tumors: A Bioinformatics Analysis

Abstract

Abstract Background. Delta-aminolevulinic acid dehydratase (δ-ALAD), as a key enzyme in hemoglobin production, have been reported to be an endogenous inhibitor of proteasomerecently. Abnormal ALAD expression was discovered in several forms of cancer, however, the role of ALAD in tumor progression remains unclear. Methods. ALAD mRNA expression were analyzed through GEPIA, UALCAN online and GEO database in primary solid tumors, respectively. Overall survival was estimated with Kaplan–Meier plotter database in these tumors. Differentially expressed genes regulated by ALAD were discovered with the LinkedOmics database in breast and lung cancer, and then the key genes were screened by hub gene analysis. Their biological function were analyzed by Gene Ontology (GO) terms analysis and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analysis. Gene set enrichment analysis (GSEA) and in vitro experiments were used to verify the role of ALAD in cell cycle and apoptosis. The correlation of ALAD expression with immune cell infiltration and biomarkers of immune cells were identified by TIMER database. Results. The results showed that ALAD mRNA expression were significantly downregulated in most of primary solid tumors. Low expression of ALAD predicts worse overall survival. 240 genes related to ALAD were discovered to participate in transcriptional regulation through functional analysis. 9 hub gene showed that it was mainly enriched in cytosol and ubiquitin-protein transferase activity using GO analysis. High expression of ALAD can induce cell cycle arrest and apoptosis according to GSEA analysis and in vitro flow cytometry analysis and annexin V staining. TIMER results showed that ALAD was significantly associated with immune cell infiltration. Conclusions. Our study demonstrated for the first time that ALAD is downregulated and low expression of ALAD is associated with worse OS in multiple solid tumors. Vitro experiment showed that ALAD high expression can suppress tumor cell cycle process and promote apoptosis in breast and lung cancer. Furthermore, we first time analyzed the tumor immune effect of ALAD in multiple solid tumors, and these findings support that ALAD is positively linked to immune cell infiltration. To sum up, it indicates that ALAD may be a valuable prognostic biomarker of solid tumors.