Possible prognostic impact of PKCι genetic variants in prostate cancer

• Published in: Cancer cell international 2024-01, Vol.24 (1), p.24-24, Article 24
• Main Authors: Hafeez, Amna, Shabbir, Maria, Khan, Khushbukhat, Trembley, Janeen H, Badshah, Yasmin, Zafar, Sameen, Shahid, Kanza, Shah, Hania, Ashraf, Naeem Mahmood, Hamid, Arslan, Afsar, Tayyaba, Almajwal, Ali, Marium, Afifa, Razak, Suhail
• Format: Article
• Language: English
• Subjects: Cell division; Epithelial cells; Genetic diversity; Genomes; Genotype & phenotype; Kinases; Malignancy; Metastasis; Molecular dynamic simulations; Mutagenesis; Mutants; Pathways; PKCι; Prostate cancer; Protein interaction; Proteins; Single-nucleotide polymorphism; Software; Statistical analysis
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-023-03182-4

Single nucleotide polymorphisms (SNPs) have been linked with prostate cancer (PCa) and have shown potential as prognostic markers for advanced stages. Loss of function mutations in PKCι have been linked with increased risk of malignancy by enhancing tumor cell motility and invasion. We have evaluated the impact of two coding region SNPs on the PKCι gene (PRKCI) and their prognostic potential. Genotypic association of non-synonymous PKCι SNPs rs1197750201 and rs1199520604 with PCa was determined through tetra-ARMS PCR. PKCι was docked with interacting partner Par-6 to determine the effect of these variants on PKCι binding capabilities. Molecular dynamic simulations of PKCι docked with Par-6 were performed to determine variant effects on PKCι protein interactions. The possible impact of changes in PKCι protein interactions on epithelial cell polarity was hypothesized. PKCι rs1199520604 mutant genotype TT showed association with PCa (p = 0.0055), while rs1197750201 mutant genotype AA also showed significant association with PCa (P = 0.0006). The binding interaction of PKCι with Par-6 was altered for both variants, with changes in Van der Waals energy and electrostatic energy of docked structures. Genotypic analysis of two non-synonymous PKCι variants in association with PCa prognosis was performed. Both variants in the PB1 domain showed potential as a prognostic marker for PCa. In silico analysis of the effect of the variants on PKCι protein interactions indicated they may be involved in PCa progression through aberration of epithelial cell polarity pathways.