Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma

Areeba Rehman; Maria Shabbir; Yasmin Badshah; Khushbukhat Khan; Janeen H Trembley; Naeem Mahmood Ashraf; Tayyaba Afsar; Ali Almajwal; Nawaf W Alruwaili; Ali Alshamari; Tariq Nahar Alanezi; Suhail Razak

doi:10.1186/s12885-023-10618-7

Elucidating the role of missense SNP of protein kinase C epsilon in HCV-induced hepatocellular carcinoma

BMC Cancer. 2023 Feb 13;23(1):147. doi: 10.1186/s12885-023-10618-7.

Authors

Affiliations

¹ Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
² Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan. mshabbir@asab.nust.edu.pk.
³ Minneapolis VA Health Care System Research Service, Minneapolis, MN, USA.
⁴ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
⁵ Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
⁶ School of Biochemistry & Biotechnology, University of the Punjab, Lahore, Pakistan.
⁷ Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
⁸ College of Medicine, King Saud University, 11481, Riyadh, Saudi Arabia.
⁹ Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. smarazi@ksu.edu.sa.

Abstract

Background: The protein kinase C (PKC) family of serine/threonine kinases contains more than ten isozymes that are involved in multiple signaling pathways, including cell cycle regulation and carcinogenesis. The PKCε isozyme is an oncogene known to be upregulated in various signaling pathways involved in hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC). However, there is no known association of missense SNPs in PKCε with this disease, which can be a potential biomarker for early diagnosis and treatment. This research reveals a novel missense SNP in PKCε that is associated with HCV-induced HCC in the Pakistani population.

Methods: The PKCε SNP with amino acid substitution of E14K was chosen for wet lab analysis. Tetra ARMS-PCR was employed for the identification of high-risk SNP in PKCε of HCV-induced HCC patients. Liver function testing was also performed for comparison between the liver condition of the HCC patient and control group, and the viral load of HCC patient samples was evaluated to determine any alteration in the viral infectivity between different genotypes of the selected high-risk PKCε variant SNP.

Results: Frequency distribution of the homozygous GG genotype was found to be highest among HCV-induced HCC patients and was also found to be significantly associated with disease development and progression. The p values of comparative data obtained for the other two genotypes, heterozygous AG and homozygous AA, of the SNP also showed the significance of the data for these alleles. Still, their odds ratio and relative risk analysis did not indicate their association with HCV-induced HCC.

Conclusion: The distribution of a genotype GG of PKCε has been found in HCV- induced HCC patients. Therefore, these PKCε SNP have the potential to be biomarkers for HCV-induced HCC. Further investigation using a larger sample size would provide additional insight into these initial data and open a new avenue for a better prognosis of this disease.

Keywords: Hepatitis C virus (HCV); Hepatocellular carcinoma (HCC); Protein kinase C (PKC); Single nucleotide polymorphism (SNP).

MeSH terms

Carcinoma, Hepatocellular* / pathology
Carcinoma, Hepatocellular* / virology
Case-Control Studies
Genetic Predisposition to Disease
Genotype
Hepacivirus
Hepatitis C* / complications
Hepatitis C* / genetics
Humans
Liver Neoplasms* / pathology
Liver Neoplasms* / virology
Mutation, Missense
Polymorphism, Single Nucleotide
Protein Kinase C-epsilon* / genetics

Substances

Protein Kinase C-epsilon
PRKCE protein, human