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Abstract
Hepatocellular carcinoma is a leading cause of cancer-related deaths due to its complexity in diagnosis, chemo-resistance, and aggressive nature. Identifying pathogenic single nucleotide polymorphism (SNP) in protein kinase C iota (PKCι) can be a potential biomarker in the prognosis and treatment of HCC. This study investigated the association between a SNP in PRKCI and the Pakistani population's hepatocellular carcinoma (HCC) risk. Obtained samples were first evaluated for ALT measurements and viral load quantification through reverse transcriptase-PCR. The PKCι nsSNP rs1199520604 was evaluated computationally by multiple consensus bioinformatics tools for predicting its potential deleterious effects. Its association with hepatitis C virus- (HCV) mediated HCC was then investigated through ARMS-PCR (Amplification Refractory Mutation System Polymerase Chain Reaction). SNP analysis of rs1199520604 was performed in 100 cases and 100 controls. Variant rs1199520604’s homozygous T genotype is a risk factor allele for the HCV-induced HCC (odds ratio: 4.13, relative risk: 2.01, P-value < 0.0001). The heterozygous genotype is determined to protect HCV patients from HCC development (P < 0.001). The study highlighted the disease association of variant rs1199520604 with HCV-induced HCC in the Pakistani populations. This variant, after further validation through high-throughput investigation on a larger cohort, has the potential to be translated at the clinical level.
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Details
1 National University of Sciences and Technology (NUST), Department of Healthcare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences (ASAB), Islamabad, Pakistan (GRID:grid.412117.0) (ISNI:0000 0001 2234 2376)
2 Minneapolis VA Health Care System, Research Service, Minneapolis, USA (GRID:grid.410394.b) (ISNI:0000 0004 0419 8667); University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657); University of Minnesota, Masonic Cancer Center, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657)
3 University of the Punjab, School of Biochemistry and Biotechnology, Lahore, Pakistan (GRID:grid.11173.35) (ISNI:0000 0001 0670 519X)
4 Agricultural Research Institute, Tarnab, Peshawar, Pakistan (GRID:grid.412117.0)
5 King Saud University, Department of Community Health Sciences, College of Applied Medical Sciences, Riyadh, Saudi Arabia (GRID:grid.56302.32) (ISNI:0000 0004 1773 5396)
6 King Saud University, College of Nursing, Sciences, Riyadh, Saudi Arabia (GRID:grid.56302.32) (ISNI:0000 0004 1773 5396)