Abstract:
Background: HCC is a major health concern worldwide. PKC gamma, a member of the conventional PKC subclass,
is involved in many cancer types, but the protein has received little attention in the context of single nucleotide
polymorphisms and HCC. Therefore, the study aims to investigate the association of PKC gamma missense SNP with
HCV-induced hepatocellular carcinoma.
Methods: The PKC gamma nsSNPs were retrieved from the ENSEMBL genome browser and the deleterious nsSNPs
were filtered out through involvingPredictSNP2, CADD, DANN, FATHMM, FunSeq2 and GWAVA. Among the filtered
nsSNPs, nsSNP rs1331262028 was identified to be the most pathogenic one. Through involving I-TASSER, ProjectHOPE,
I-Mutant, MUpro, mCSM, SDM, DynaMut and MutPred, the influence of SNP rs1331262028 on protein structure, function
and stability was estimated. A molecular Dynamic simulation was run to determine the conformational changes
in mutant protein structure compared to wild. The blood samples were collected for genotyping analysis and for
assessing ALT levels in the blood.
Results: The study identified for the first time an SNP (rs1331262028) of PRKCG to strongly decrease protein stability
and induce HCC. The RMSD, RMSF, and Rg values of mutant and wild types found were significantly different. Based
on OR and RR values of 5.194 and 2.287, respectively, genotype analysis revealed a higher correlation between the
SNP homozygous wild Typeform, AA, and the disease while patients with genotype AG have higher viral load.
Conclusion: Outcomes of the current study delineated PKC gamma SNP rs1331262028 as a genetic marker for HCVinduced
HCC that could facilitate disease management after further validation.
