Abstract:
The cancer that is commonly diagnosed all over the world is breast cancer, with an
estimated 2.26 million cases recorded in 2020. It is the main cause of death in women.
In past eras, the role of different genes including TP53, PTEN, STK11, CDH1, ATM,
PALB2, CHEK2, and BRCA1 and BRCA2 in breast cases have been studied and
identified, but the result was not effective for treatment and diagnosis at an early stage
of breast cancer. Therefore, there is a need for another novel gene for early prognosis
and better treatment for breast cancer. For this purpose, novel KPC family isoforms are
preferable as a potential molecular target, which lower the incidence rate and recurrence
of breast cancer. The KPCQ is a member of novel KPCs and belongs to serine
/threonine kinase. KPCQ plays an important role in the pathophysiology of numerous
cancers, particularly autoimmune diseases, and various cancers. The determination of
the impact of missense SNPs on the structure and function of the KPCQ gene and the
identification of a novel KPCQ missense variant’s association with Breast cancer and
its clinical features is the main purpose of the study. In this study, KPCQ variant C29Y
was selected, and this variant was further analyzed to validate their effect on function,
structure, and stability of protein through experimental and in vitro analysis and these
predict that protein structure alters and then leads to the progression of breast cancer.
Further, genotyping analysis was performed to confirm the association of this variant
with breast cancer and this analysis confirmed that the C29Y variant of KPCQ was
involved in the progression of breast cancer. The molecular dynamic simulation was
performed which proved that this variant of KPCQ is linked with the progression of
breast cancer. As a result, this study laid the foundations for considering the variant
rs1248923790 as a predictive prognostic biomarker for breast cancer. It could be used
at the clinical level after more validation.
