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.

Details

Title
Investigating pathogenic SNP of PKCι in HCV-induced hepatocellular carcinoma
Author
Khan, Naila 1 ; Khan, Khushbukhat 1 ; Badshah, Yasmin 1 ; Trembley, Janeen H. 2 ; Ashraf, Naeem Mahmood 3 ; Shabbir, Maria 1 ; Danish, Lubna 4 ; Afsar, Tayyaba 5 ; Almajwal, Ali 5 ; Justin, Saira 1 ; Hasan, Zafarul 6 ; Razak, Suhail 5 

 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) 
 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) 
 University of the Punjab, School of Biochemistry and Biotechnology, Lahore, Pakistan (GRID:grid.11173.35) (ISNI:0000 0001 0670 519X) 
 Agricultural Research Institute, Tarnab, Peshawar, Pakistan (GRID:grid.412117.0) 
 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) 
 King Saud University, College of Nursing, Sciences, Riyadh, Saudi Arabia (GRID:grid.56302.32) (ISNI:0000 0004 1773 5396) 
Pages
12504
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2844937486
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.