Unveiling Genetic Biomarkers: The Role of rs749937042 and CYP2C9 in Hepatocellular Carcinoma Development
محل انتشار: دومین کنگره بین المللی کنسرژنومیکس
سال انتشار: 1403
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 57
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شناسه ملی سند علمی:
ICGCS02_347
تاریخ نمایه سازی: 17 دی 1403
چکیده مقاله Unveiling Genetic Biomarkers: The Role of rs749937042 and CYP2C9 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 GSE14520 from the Gene Expression Omnibus (GEO), utilizing the GPL571 platform for analysis. The dataset was analyzed using GEO2R, leading to the selection of CYP2C9, one of the most significantly down-regulated genes (logFC = -3.366, adj.p.val = 1.63e-21). Validation of the adjusted p-value and log fold change was performed using GEPIA2 and ENCORI online software. Subsequently, one SNP was selected from miRNASNP, which is associated with microRNA. The relationship between the selected miRNA and CYP2C9 was further analyzed using ENCORI. ▎Results Our analysis revealed a significant relationship between rs749937042 and CYP2C9 in LIHC. This SNP appears to facilitate the binding of hsa-miR-139-5p to CYP2C9. miRNA analysis via ENCORI demonstrated significant down-regulation (FC = 0.31, p-value = 1.8e-27), survival implications (p-value = 3.4e-6, coef = -0.84, HR = 0.43), and correlation (coefficient-R = 0.353, p-value = 2.66e-12) with the selected gene, suggesting an increased probability of developing LIHC. Additionally, we identified a connection among CYP2C9, rs749937042, 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 rs749937042 and CYP2C9 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 rs749937042 and CYP2C9 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.
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نویسندگان مقاله Unveiling Genetic Biomarkers: The Role of rs749937042 and CYP2C9 in Hepatocellular Carcinoma Development
Zahra Arab Bafrani
Islamic Azad University, Najafabad
Mohammad Rezaei
Department of Biology and Biotechnology, University of Pavia, Pavia, Italy
Hossein Salehi Pour
Islamic Azad University, Najafabad
Mansoureh Azadeh
Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran