Correlations of pri-Let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer after transcatheter arterial chemoembolization

Abstract

Background and aim: Single nucleotide polymorphisms (SNPs) within miRNAs could change their production or affinity with target genes, thus leading to malignant diseases. This study aims to explore correlations of pri-let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer (PLC) after a transcatheter arterial chemoembolization (TACE) surgical procedure.

Materials and methods: A total of 302 PLC patients treated with hepatoprotective therapies after TACE were selected to and assigned into recurrent and non-recurrent groups. Genotypes of pri-let-7a-1 rs1073997 and pri-let-7a-2 rs629367 were analyzed by Taqman assay. The relationship between PLC with the mutation of each SNP was determined by a multivariate logistic regression analyses. Moreover, the association between survival and pri-let-7 gene polymorphisms was analyzed by the Kaplan-Meier method. The Progress Free Survival (PFS) curve, correlation of pri-let-7a-1 rs629367 with alcohol, HBsAg-positive and TNM III/IV were analyzed by a stratified analysis. Additionally, the risk factors for the recurrence of PLC were analyzed by a multivariate logistic regression analyses.

Results: Results showed that the allelic frequency of the pri-let-7a-2 rs629367 SNP in the recurrent group was higher than that of the non-recurrent group. The distribution of CC genotype was significantly higher than non-CC genotype in the recurrent group. Alcohol consumption, positive expression of hepatitis B surface antigen (HBsAg), AC + CC genotype of rs629367 and TNM III/IV were determined to be the risk factors for the recurrence and metastasis of PLC after TACE. We found a positive correlation between pri-let-7a-2 rs629367 with alcohol consumption, HBsAg-positive and TNM III/IV. The median PFS of HBsAg-positive and TNM III/IV patients with the AC + CC genotype of rs629367 was shorter than those with non-AC + CC genotype.

Conclusion: Our findings provide evidence that patients with PLC that carry the AC + CC genotype of pri-let-7a-2 rs629367 after TACE have a worse prognosis than those who carry the AA genotype. We speculate that the pri-let-7 rs629367 SNP could be used as a predictor of recurrence and metastasis after TACE for patients with PLC.

Keywords: Metastasis; Pri-let-7a-1 rs10739971; Pri-let-7a-2 rs629367; Primary liver cancer; Recurrence; Transcatheter arterial chemoembolization.