Unveiling Genetic Biomarkers: The Role of rs۷۴۹۹۳۷۰۴۲ and CYP۲C۹ in Hepatocellular Carcinoma Development

Background Liver hepatocellular carcinoma (LIHC) is a leading cause of cancer-related mortality worldwide, marked by a notably poor prognosis. The five-year relative survival rate for LIHC patients remains alarmingly low, highlighting an urgent need for enhanced diagnostic and prognostic strategies. This study aims to improve disease prognosis by identifying reliable biomarkers, specifically focusing on single nucleotide polymorphisms (SNPs). By utilizing advanced bioinformatics tools, we aim to uncover novel SNPs that could serve as potential biomarkers for LIHC, integrating genomic data and computational analyses to provide insights into the genetic underpinnings of hepatocellular carcinoma. This may ultimately lead to better risk stratification and targeted therapeutic approaches. ▎Method and Materials We began by downloading the suitable dataset GSE۱۴۵۲۰ from the Gene Expression Omnibus (GEO), utilizing the GPL۵۷۱ platform for analysis. The dataset was analyzed using GEO۲R, leading to the selection of CYP۲C۹, one of the most significantly down-regulated genes (logFC = -۳.۳۶۶, adj.p.val = ۱.۶۳e-۲۱). Validation of the adjusted p-value and log fold change was performed using GEPIA۲ and ENCORI online software. Subsequently, one SNP was selected from miRNASNP, which is associated with microRNA. The relationship between the selected miRNA and CYP۲C۹ was further analyzed using ENCORI. ▎Results Our analysis revealed a significant relationship between rs۷۴۹۹۳۷۰۴۲ and CYP۲C۹ in LIHC. This SNP appears to facilitate the binding of hsa-miR-۱۳۹-۵p to CYP۲C۹. miRNA analysis via ENCORI demonstrated significant down-regulation (FC = ۰.۳۱, p-value = ۱.۸e-۲۷), survival implications (p-value = ۳.۴e-۶, coef = -۰.۸۴, HR = ۰.۴۳), and correlation (coefficient-R = ۰.۳۵۳, p-value = ۲.۶۶e-۱۲) with the selected gene, suggesting an increased probability of developing LIHC. Additionally, we identified a connection among CYP۲C۹, rs۷۴۹۹۳۷۰۴۲, and the c-Fos protein in the Enrichr database, indicating that mutations in this gene may play a crucial role in the carcinogenesis of hepatocellular carcinoma. ▎Conclusion Our findings indicate that the down-regulation of rs۷۴۹۹۳۷۰۴۲ and CYP۲C۹ may significantly contribute to the development and progression of hepatocellular carcinoma (LIHC). The correlation between these genetic factors suggests they could increase the risk of LIHC by interfering with c-Fos protein expression, which is involved in cellular proliferation and oncogenesis. These insights underscore the potential of rs۷۴۹۹۳۷۰۴۲ and CYP۲C۹ as biomarkers for LIHC, paving the way for further research into targeted therapies and personalized treatment strategies. Understanding these molecular interactions could ultimately enhance prognostic tools and therapeutic interventions for patients at risk of developing hepatocellular carcinoma.

کلیدواژه ها:

Liver hepatocellular carcinoma(LIHC) ، Hepatocellular Carcinoma(HCC) ، CYP۲C۹ gene ، rs۷۴۹۹۳۷۰۴۲ ، c-Fos protein