Potentially functional genetic variants of the N7-methylguanosine modification LARP1 gene predict hepatitis B virus-related hepatocellular carcinoma survival

Abstract

Abstract Background N7-methylguanosine (m7G) modification is an important RNA modification, which plays a key role in tumorigenesis and progression. However, few studies have explored the effects of genetic variants in m7G modification genes on survival of patients with hepatocellular carcinoma (HCC). Methods We used multivariable Cox proportional hazards regression to evaluate associations between genetic variants in 28 m7G modification genes and overall survival (OS) of 866 hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) patients. Results In the present study, we identified that two potentially functional single nucleotide polymorphisms (SNPs) in LARP1 (rs12055336 G > C and rs6580113 G > C) were associated with OS of HBV-HCC patients, with an adjusted hazards ratio (HR) of 1.24 (95% confidence interval[CI] = 1.06–1.45, P = 0.008) and 0.83 (95% CI = 0.72–0.96, P = 0.011), respectively. The number of risk genotypes of these two SNPs showed a significant association with a poor survival of HBV-HCC patients (Ptrend=0.004). Expression quantitative trait loci (eQTL) analysis demonstrated that LARP1 rs12055336 C allele was associated with elevated mRNA expression levels in 670 whole blood samples in Genotype-Tissue Expression (GTEx) (P < 0.001), but not in 1000 Genomes Project. In addition, LARP1 rs6580113 C allele was associated with decreased mRNA expression levels in whole blood samples in GTEx (P < 0.001) and 76 lymphoblastoid cells samples in 1000 Genomes Project (P = 0.049). Furthermore, compared with adjacent normal tissues, LARP1 mRNA expression levels were higher in HCC tissues and were associated with a poorer OS of HCC patients. Conclusions These findings suggest that genetic variants of the m7G modification LARP1 gene may be predictors for HBV-HCC survival, likely by regulating the mRNA expression of corresponding gene.