Abstract
BackgroundPrevious reports have shown that short/branched chain acyl-CoA dehydrogenase (ACADSB) plays an important role in glioma, but its role in clear cell renal carcinoma (ccRCC) has not been reported.MethodsThe TIMER and UALCAN databases were used for pan-cancer analysis. RNA sequencing and microarray data of patients with ccRCC were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus database. The differential expression of ACADSB in ccRCC and normal kidney tissues was tested. Correlations between ACADSB expression and clinicopathological parameters were assessed using the Wilcoxon test. The influences of ACADSB expression and clinicopathological parameters on overall survival were assessed using Cox proportional hazards models. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different ACADSB expression phenotypes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on genes with similar expression patterns to ACADSB. Correlations between ACADSB and ferroptosis-related genes were assessed using Spearman’s correlation analysis.ResultsPan-cancer analysis revealed that ACADSB is down-regulated in multiple cancers, and decreased expression of ACADSB correlates with poor prognosis in certain types of cancer. Differential expression analyses revealed that ACADSB was down-regulated in ccRCC, indicating that ACADSB expression could be a single significant parameter to discriminate between normal and tumor tissues. Clinical association analysis indicated that decreased ACADSB expression was associated with high tumor stage and grade. The Cox regression model indicated that low ACADSB expression was an independent risk factor for the overall survival of patients with ccRCC. GSEA showed that 10 gene sets, including fatty acid (FA) metabolism, were differentially enriched in the ACADSB high expression phenotype. GO and KEGG pathway enrichment analysis revealed that ACADSB-related genes were significantly enriched in categories related to FA metabolism, branched-chain amino acid (BCAA) metabolism, and iron regulation. Spearman’s correlation analysis suggested that the expression of ACADSB was positively correlated with the expression of ferroptosis driver genes.ConclusionsACADSB showed good diagnostic and prognostic abilities for ccRCC. The downregulation of ACADSB might promote tumorigenesis and tumor progression by inhibiting FA catabolism, BCAA catabolism, and ferroptosis in ccRCC.
Highlights
Short/branched chain acyl-CoA dehydrogenase (ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes, which is involved in the metabolism of fatty acids (FAs) and branch-chained amino acids (BCAAs) [1]
Differential expression analysis using tumor immune estimation resource database (TIMER) showed that ACADSB is down-regulated in multiple types of cancer, including bladder cancer (BLCA), breast cancer (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), thyroid carcinoma (THCA), and uterine corpus endometrial carcinoma (UCEC; Figure 1A)
Proteome data derived from the UALCAN database suggest that ACADSB is down-regulated in breast cancer, colon cancer, clear cell renal cell carcinoma (ccRCC), and UCEC (Figure 1B)
Summary
Short/branched chain acyl-CoA dehydrogenase (ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes, which is involved in the metabolism of fatty acids (FAs) and branch-chained amino acids (BCAAs) [1]. Previous studies have revealed that ACADSB plays an important role in glioma, colorectal cancer (CRC), and hepatocellular carcinoma (HCC) [2–5]. The role of ACADSB in clear cell renal cell carcinoma (ccRCC) has not yet been reported. CcRCC is the most common and aggressive type of renal cell carcinoma (RCC), which accounts for approximately 3% of all cancers and is the third most common malignancy of the urinary system [6, 7]. Targeted therapy and immune checkpoint inhibitor-based immunotherapy have substantially improved the outcomes of patients with advanced ccRCC over the past decade. The aim of this study was to explore the potential diagnostic and prognostic roles of ACADSB in ccRCC. Previous reports have shown that short/branched chain acyl-CoA dehydrogenase (ACADSB) plays an important role in glioma, but its role in clear cell renal carcinoma (ccRCC) has not been reported
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