Prognostic Significance of KPCH Missense Variants on Breast Cancer

Abstract

Breast cancer is the leading cause of death in women worldwide. The previous biomarkers have not shown promising results in treating this disease, but this problem can be solved by Kinase Protein C and its isozymes. KPCH a member of the KPC family has been linked to other cancers. Previously, little work has been done to find the single nucleotide polymorphism that is linked to Breast cancer. Therefore, the study aims to study the effect of missense variants on the structure and function of novel KPCH and to detect the missense variants associated with breast cancer and its pathological and clinical parameters. The missense variants of KPCH were recovered from the ENSEMBL genome browser. Then the pathogenicity of the deleterious variants was checked through six different consensus tools. Some other in silico tools were used to find the association of deleterious SNPs with the KPCH protein function, stability, and structure. To identify the change in the structure and conformation of the wildtype and mutant protein structure molecular dynamic simulation was performed. The genotype analysis was performed after collecting the blood samples. The results revealed that the most pathogenic SNP among all the missense variants was rs752329416 (R596C). The wild type structure of KPCH and the mutant R596C structure has shown significant results for RMSF, RMSD, Rg, and SASA. The genotype analysis has shown the association between the variant rs752329416 and breast cancer as the genotypes CC and TT have shown significant P-values. This current study represents the KPCH SNP rs752329416 as a potential biomarker for Breast cancer. Further analysis will help in the therapy and diagnosis of the disease