Investigating KPCZ pathogenicity in human breast cancer

Abstract

Breast cancer is a leading cause of mortality among women worldwide, and while numerous biomarkers have been identified for detection and treatment, there is a continuous need for novel and more efficacious biomarkers. Kinase Protein C Zeta (KPCZ) is a protein associated with cancer development and has been implicated in multiple cancer signaling pathways. This study aims to investigate the pathogenicity of KPCZ in human breast cancer by analyzing single nucleotide polymorphisms (SNPs), predicting its three-dimensional structure, examining sub-cellular localization, and assessing interactions with other proteins. By analyzing genotyping data from breast cancer patients and healthy individuals, the study identifies the association of pathogenic non-synonymous (rs367917640) KPCZ SNPs with breast cancer where homozygous AA genotype showed association with breast cancer with its highest frequency distribution in patient samples. Furthermore, this study examines the trends in relative expression of KPCZ, EGF, and NFkB biomarkers, as well as their correlation with various clinical features and risk factors associated with breast cancer. It reveals that KPCZ plays a significant role in cancer development, with its overexpression is linked to breast carcinogenesis. MD Simulations revealed that docking structure of G65A mutated complex with PDK1 showed a more stable confirmation as compared to the wildtype KPCZ complex