Evaluating Pathogenic Effect of KLF12 Polymorphism on Hepatocellular Carcinoma

Abstract

Liver cancer is the third most common cause of death globally, accounting for 7.8% of deaths by cancer. Early-stage liver cancer is frequently asymptomatic and aggressive, hindering the timely and effective diagnostic and prognostic approach. Diagnosis at an advanced stage frequently makes liver cancer less curable as it exhibits drug resistance. The 5-year survival rate in liver cancer patients is low, thus incidence and mortality rates regarding liver cancer are growing exponentially across the world. However, there is a need to explore new diagnostic and prognostic targets to aid the early diagnosis and effective treatment of liver cancer. Many SNPs in genes such as PRKCγ, HJURP, TERT, TLR3, TLR4 and TP53 have been linked to liver cancer. KLF12 belongs to the KLF family family consists of three highly conserved 2cystine-2histidine (C2H2) type zinc finger domains and acts as a transcription factor. KLF12 bind at the target genes and act as a transcription suppressor. KLF12 target genes are involved in cell cycle regulation, cell proliferation, cellular growth, and apoptosis. KLF12’s role has been explored in multiple cancers, but the protein has little attention in the context of evaluating single nucleotide polymorphisms (SNPs). The purpose of this study is to investigate KLF12 SNPs pathogenicity and establish a relation to liver cancer susceptibility, development, and progression. Various in silico tools were employed to investigate SNP variants’ effect on KLF12 protein stability, and structural and functional alterations. The most pathogenic SNP variant rs1257857115 (R397W) genotypes were investigated in 100 HCC patients and 100 healthy controls by employing tetra ARMS PCR. The SNPs in KLF12 affect the protein’s stability, structure, and function. There was a positive association between KLF12 variant rs1257857115 genotype (TT) and liver cancer with higher susceptibility risk, in contrast, the protective role of wildtype genotype (CC) was found in healthy controls. As a result, the findings suggest that KLF12 variant ID rs1257857115 was significantly found in liver cancer patients and could be used as a diagnostic biomarker in liver cancer.