Genetic Variant in KPCE Gene: A Possible Genetic Marker for Cervical Cancer

Abstract

Cervical cancer is one of the most prevalent types of gynaecological malignancy in women around the globe. Along with the HPV infections several genetic players are also involved in the onset and progression of cervical cancer. KPCE is an isoform in the novel-KPC subfamily of AGC-kinases that plays a crucial role in the development of different cancers. Various studies have shown that genetic variants in KPCE are associated with several ailments including cancers as a result of their altered structural and functional profile. Till this date, no data has been published that has elucidated the impact of KPCE genetic variants in association with cervical cancer. Therefore, the objectives of this study are to identify novel pathogenic genetic variants in KPCE and explore their impact on protein structure, function, stabilization, and molecular interactions with one of Its target proteins which is Smad3 in this study. Moreover, this study also intended to explore the role of those variants with cervical cancer through genotype analysis. This study has revealed that KPCE genetic variants rs1553369874 and rs1345511001 in the regulatory C2-like domain have an association with the risk of cervical cancer development. Interaction dynamics analysis has proved that KPCE variant structures and Smad3 interact in an aberrant manner compared to native KPCE – Smad3 interaction, which might lead to the activation of Warburg`s effect and angiogenesis. Data obtained from this research can be potentially used for the development of novel therapeutic targets for better treatment options against cervical cancer as well as the novel biomarkers for early diagnosis and better prognosis