Polymorphisms in TRAIL predict long-term survival and extrahepatic recurrence following initial hepatectomy for hepatocellular carcinoma.

BACKGROUND: Liver natural killer (NK) cells are the first cells to respond to infections and malignancies, such as intraoperative tumor spill. Liver NK cells express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a marker for hepatocellular carcinoma (HCC). However, the influence of TRAIL single-nucleotide polymorphisms (SNPs) on hepatectomy patients with HCC remains unclear.

METHODS: Here, we investigated TRAIL SNPs (rs1131568, rs1131579, and rs1131580) located at positions 1525, 1588, and 1595 of exon 5 of the TNFSF10 gene. A total of 104 HCC patients who underwent initial hepatectomy were analyzed. Kaplan-Meier survival analysis and Cox proportional hazard regression were conducted to evaluate the associations between TRAIL genotypes and clinical HCC outcomes.

RESULTS: Patients harboring the homozygous AA genotype of TRAIL SNPs rs1131568 and rs1131579 and the TT genotype of the TRAIL SNP rs1131580 had lower overall survival and higher rates of extrahepatic recurrence (EHR) than patients harboring the wild type or heterozygous genotypes. Moreover, univariate and multivariate Cox regression analysis revealed that the homozygous genotypes of the target TRAIL SNPs were independent predictive factors for EHR after initial hepatectomy for HCC.

CONCLUSION: Our findings revealed that the homozygous genotypes of TRAIL SNPs are independent predictors of EHR in initial hepatectomy patients with HCC.