Mechanistic Impact of KLF15 Polymorphism and its association with Liver Cancer

Abstract

As liver cancer ranks among the top cancer-related fatalities worldwide, prognostic indicators and treatment targets for this disease need to be improved. This study attempts to ascertain whether the Krüppel-like factor 15 (KLF15) gene and its variants are linked to liver cancer through use of in-silico and lab-based analysis. Using in silico techniques including SIFT, PolyPhen, CADD, REVEL, Mutation Assessor, MetaLR, MutPred2, DynaMut, MUpro, MAESTRO, Project HOPE, and FATHMM, two pathogenic missense variants rs7557194 and rs7686768 were identified. Structural and functional analyses suggest that these variants most likely disrupt the protein's structure and function. Following statistical analysis and tetra ARMS-PCR investigation, it became apparent that in a population from Pakistan the rs7557194 variant was notably linked to liver cancer. The study underlines that a target for treatment and a marker for liver cancer diagnosis could be the R364P mutation of KLF-15. These findings show the potential for the use of the KLF15 R364P mutation as a liver cancer biomarker, therefore enabling more precise treatments and improved diagnostics. Future research with larger sample sizes and different populations should investigate the functional mechanisms of KLF15 variants in liver cancer progression utilizing in vitro and in vivo studies, therefore validating our results.