The promising novel biomarkers and candidate small molecule drugs in kidney renal clear cell carcinoma: Evidence from bioinformatics analysis of high‐throughput data

Abstract

Background Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal tumor. However, the molecular mechanisms of KIRC pathogenesis remain little known. The purpose of our study was to identify potential key genes related to the occurrence and prognosis of KIRC, which could serve as novel diagnostic and prognostic biomarkers for KIRC. Methods Three gene expression profiles from gene expression omnibus database were integrated to identify differential expressed genes (DEGs) using limma package. Enrichment analysis and PPI construction for these DEGs were performed by bioinformatics tools. We used Gene Expression Profiling Interactive Analysis (GEPIA) database to further analyze the expression and prognostic values of hub genes. The GEPIA database was used to further validate the bioinformatics results. The Connectivity Map was used to identify candidate small molecules that could reverse the gene expression of KIRC. Results A total of 503 DEGs were obtained. The PPI network with 417 nodes and 1912 interactions was constructed. Go and KEGG pathway analysis revealed that these DEGs were most significantly enriched in excretion and valine, leucine, and isoleucine degradation, respectively. Six DEGs with high degree of connectivity ( ACAA1, ACADSB, ALDH6A1, AUH, HADH, and PCCA ) were selected as hub genes, which significantly associated with worse survival of patients. Finally, we identified the top 20 most significant small molecules and pipemidic acid was the most promising small molecule to reverse the KIRC gene expression. Conclusions This study first uncovered six key genes in KIRC which contributed to improving our understanding of the molecular mechanisms of KIRC pathogenesis. ACAA1, ACADSB, ALDH6A1, AUH, HADH, and PCCA could serve as the promising novel biomarkers for KIRC diagnosis, prognosis, and treatment.

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

“…ACAA1 gene encodes acetyl-CoA acyltransferase 1 (ACAA1), another important enzyme during peroxisomal β-oxidation of fatty acids (Antonenkov et al, 1997). In previous studies, it was demonstrated to be under-expressed in liver cancer (Yan et al, 2017) and kidney renal clear cell carcinoma (Zhang et al, 2019). Here, similar to HSD17B4, ACAA1 was also found to be down-regulated and negatively correlated with MKI67 expression in NSCLC, indicating its anti-tumor potential.…”

ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells

“…As a member of the acyl-CoA dehydrogenase family, ACADSB promotes the lipid metabolism via catalyzing the dehydrogenation of acyl-CoA derivatives (Arden et al, 1995). Earlier studies indicated that ACADSB might exert tumor suppressive function in poorly-differentiated hepatocellular carcinoma and kidney renal clear cell carcinoma (Nwosu et al, 2018;B. Zhang et al, 2019).…”

RNA Sequencing of Collecting Duct Renal Cell Carcinoma Suggests an Interaction between miRNA and Target Genes and a Predominance of Deregulated Solute Carrier Genes

“…ALDH6A1 catalyzes the oxidative decarboxylation of malonate and methylmalonate semialdehydes to acetyl-and propionyl-CoA in the valine and pyrimidine catabolic pathways [33]. Recently, Zhang et al identified six genes, including ALDH6A1, as biomarkers for ccRCC, and demonstrated that downregulation of the ALDH6A1 gene was associated with shorter overall survival of ccRCC patients in the TCGA dataset [34]. MARC2 (MOSC2) has been suggested to play a role in the mitochondrial nitric oxidase pathway and in the detoxification of xenobiotics [35].…”