Polymorphic Variants of Gene Related to Arginine Metabolism and the Risk of HCC.

Background: Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, argininosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis.

Objectives: The aim of this study is to analyze the gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population.

Method: Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between gene with other associated gene/proteins.

Results: The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in and genes was observed. Bioinformatics analysis reveals the correlation between polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results.

Conclusion: Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of might be helpful in early diagnostic and therapeutic purposes.