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.
