Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of human tumors, which is characterized by high morbidity and mortality rates. AKT1 transcriptional activity is implicated in HCC initiation and development. In the present study, the effects of rs2494752 single nucleotide polymorphism (SNP) on AKT1 transcriptional activity in the progression of HCC cells were investigated. A case-control study was analyzed in 1,056 HCC patients and 1,080 healthy individuals using the PCR assay method. Results indicated AKT1 expression levels were up-regulated in HCC tissue compared to adjacent normal tissues. Furthermore, a higher frequency of AKT rs2494752 AG and AA genotypes were observed in HCC cases (P=0.0046). Gene polymorphism identified C and T alleles were frequency in HCC patients compared to healthy individuals. Individuals harboring AKT rs2494752 AG/AA genotype had a vital increased susceptibility to HCC in the dominant model (P=0.0028). In addition, AKT1 rs2494752 GG genotype showed an increasing of AKT1 promoter activity determined by the luciferase assay. Furthermore, it was demonstrated that AKT1 rs2494752 GG and C polymorphism was more aggressive than other AKT1 rs2494752 cancer cells. Moreover, AKT1 rs2494752 GG markedly increased rates of response to NCT chemotherapy. Additionally, results revealed that AKT1 rs2494752 GG and C increased the risk factors of HCC. In conclusion, these results indicate that AKT1 rs2494752 polymorphisms may be regarded as a candidate gene in assessing the susceptibility, metastasis and responses to chemotherapy in the progression of hepatocellular carcinoma.