Table_1_Associations between genetic variants in sphingolipid metabolism pathway genes and hepatitis B virus-related hepatocellular carcinoma survival.docx

BackgroundAlthough the sphingolipid metabolism pathway is known to play a significant role in tumor progression, there have been few studies on how genetic variants in the sphingolipid metabolism pathway genes affect the survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).MethodsWe utilized available genotyping data to conduct multivariate Cox proportional hazards regression model analysis, examining the associations of 12,188 single nucleotide polymorphisms (SNPs) in 86 sphingolipid metabolism pathway genes on the survival of 866 HBV-HCC patients, and the model was also used in additive interaction analysis. We used bioinformatics functional prediction and expression quantitative trait locus (eQTL) analysis to explore the potential functions of SNPs and to evaluate the association of SNPs with the corresponding mRNA expression, respectively. We also used the online database TIMER2.0 (http://timer.comp-genomics.org/) to analyze the relationship between the corresponding mRNA expression levels and immune cell infiltration.ResultsOur study found that GBA2 rs1570247 G>A was significantly associated with elevated survival of HBV-HCC patients [(hazards ratio (HR)=0.74, 95% confidence interval (CI)=0.64-0.86, P

尽管已知鞘脂代谢途径在肿瘤进展中发挥着重要作用，但关于鞘脂代谢途径基因中的遗传变异如何影响乙型肝炎病毒（HBV）相关肝细胞癌（HCC）患者的生存情况的研究却寥寥无几。本研究中，我们利用可用的基因分型数据，通过多元Cox比例风险回归模型分析，考察了86个鞘脂代谢途径基因中的12,188个单核苷酸多态性（SNPs）与866例HBV-HCC患者生存状况之间的关联，并将模型应用于加性交互分析。我们运用生物信息学功能预测和表达数量性状位点（eQTL）分析，探究SNPs的潜在功能，并分别评估SNPs与相应mRNA表达之间的关联。此外，我们还利用在线数据库TIMER2.0（http://timer.comp-genomics.org/）分析了相应mRNA表达水平与免疫细胞浸润之间的关系。我们的研究结果表明，GBA2 rs1570247 G>A位点的基因型与HBV-HCC患者生存率的提高显著相关[风险比（HR）=0.74，95%置信区间（CI）=0.64-0.86，P值]。