CA۹ as a Biomarker in Kidney Cancer: Role in Carbonic Acid Metabolism and Regulatory RNAs

KIRC stands for "Kidney Renal Clear Cell Carcinoma", and it's the most common type of kidney cancer, accounting for about ۷۰-۸۰% of kidney cancer cases. KIRC originates from the epithelial cells that line the small tubules within the kidneys. Our study aims to find new biomarkers related to the pathway of carbonic acid metabolism through bioinformatics analysis. In this analysis, the related SNPs, lncRNAs, miRNAs, and their role in kidney cancer have been investigated. Material and Methods: In the first step, a suitable dataset (GSE۱۰۰۶۶۶) was obtained from the Gene Expression Omnibus (GEO) and analyzed using GEO۲R. The gene with the significant high expression was then selected. The p-value and logFC of this gene were checked and validated by GEPIA۲ and ENCORI. The miRNA correlated with the targeted gene was analyzed using miRWalk. Furthermore, the related signaling pathway was identified through, Enrichr, KEGG, and relevant articles, and analyzed using Reactome. The SNP located in the coding region was selected after analyzing through SIFT and dbSNP databases, and the impact of this SNP on the target gene was investigated using the HOPE database. Also, the miRWalk database was used to identify a miRNA and clarify its role in our cancer. Results: CA۹ was selected as the gene with a significantly high expression increase in KIRC (logFC:۸.۲۶, adj. p.val < ۰.۰۴). With STRING the interaction between CA۹ and other proteins that regulate PH was discovered such as HIF-۱α. By using KEGG and Reactome databases, it was demonstrated that the CA۹ gene plays a role in many biological pathways, one of the most important of which is the pathway of carbonic acid metabolism. In this pathway, CA۹ catalyzes the reversible reaction of CO۲ and water to bicarbonate and protons, and it helps to maintain acid-base balance. Also, CA۹ can promote cancer cell growth and survival by altering extracellular pH and influencing metabolic processes. A deleterious SNP(rs۷۷۹۸۴۰۴۹)(arginine to Tryptophan at position ۱۳۱.), was found by using SIFT and analyzed with HOPE databases and it showed that the mutant residue is bigger and more hydrophobic than the wild-type residue. miRNA "has-miR-۴۲۶۸" (position: ۳'UTR, energy: -۳۰.۳, bindingp: ۱, seed: ۱) (from MirWALK) and lncRNA "AIRN" (from LncRRIsearch) were also identified and may influence KIRC. Conclusion: CA۹ is a gene that is responsible for producing a protein named "carbonic anhydrase". This protein plays an important role in regulating the pH and transporting CO۲ in tissues. in addition, this gene is recognized as a biological marker in cancers, especially kidney cancer. CA۹'s function in the tumor microenvironment supports immune evasion, that critical for KIRC progression. Additionally, the lncRNA and miRNA which were found could be a suitable biomarker but it needs more research.

کلیدواژه ها:

Kidney Cancer ، CA۹ ، Biomarker ، hsa-miR-۴۲۶۸ ، miRNA analysis