A genetic variant in Long Non-Coding RNA HULC is associated with poor prognosis following the curative resection of hepatocellular carcinoma

【摘要】：Background: Hepatocellular carcinoma up-regulated long non-coding RNA(HULC) is the first discovered lncRNA with aberrantly up-regulation in HCC, promoting HCC cell proliferation, autophagy and chemoresistance of HCC. We hypothesize that genetic variant in HULC gene is associated with survival of patients with hepatocellular carcinoma(HCC) following the curative resection.Methods: In this study, we performed genotyping assays for HULC polymorphisms(rs1328866 T A,rs1328868 C T, rs7763881 A C, rs2038540 C G) in a cohort of 386 HCC patients who received curative resection. Multivariate Cox proportional hazards model and the Kaplan-Meier methods with log-rank test were used to evaluate the association between HULC SNPs and overall survival of HCC patients.Results: Results found that HULC rs7763881 was significantly associated with overall survival of HCC patients after curative resection. HCC patients carrying AC/CC genotype had a significantly increased risk of death when compared with AA genotype carrier(adjusted hazard ratio(HR) = 1.29, 95%confidence interval(CI) = 1.01-1.66, P = 0.044). Kaplan-Meier analyses showed a significantly shorter survival time in HCC patients with AC/CC genotypes of SNP rs7763881 than AA genotype carrier(30.1 months vs. 41.1 months, P log-rank = 0.033). In addition, the stratification analysis showed that compared with SNP rs7763881 AA genotype carrier, patients with CA/CC genotypes had a significantly worse overall survival particularly evident in older subjects(age ≥ 50 years), patients with BCLC stage B/C, patients with AFP level ≥ 400 ng/mL(P 0.05) and an interaction effect on overall survival of HCC between the SNP rs7763881 and age was found(P = 0.023).Conclusions: This study suggests that HULC rs7763881 might contribute to overall survival in HCC patients received curative resection, which may serve as an independent prognostic marker for HCC patients.