C型凝集素结构域家族9成员A在肝细胞癌的预后价值及其对肿瘤免疫的影响

The prognostic value of C-type lectin domain family 9A in hepatocellular carcinoma and its impact on tumor immunity

目的通过生物信息学分析C型凝集素9家族A成员(CLEC9A)在肝癌中的作用。方法下载癌症基因组图谱(TCGA)数据库的泛癌转录组数据及临床数据,明确CLEC9A在泛癌中的差异表达,继而Kaplan-Meier分析CLEC9A的表达与泛癌的总生存期和疾病特异生存期的关系,并分析CLEC9A的表达与肝癌临床病理特征的相关性。通过基因集变异分析(GSVA)和免疫组织化学方法分析验证CLEC9A在肝癌免疫微环境的作用。结果基于配对与非配对的泛癌及正常样本的差异基因分析结果,肝癌组织中CLEC9A表达水平[0.183(0.069~0.338),0.187(0.076~0.405)]明显低于癌旁组织中CLEC9A表达水平[0.343(0.242~0.515)],差异有统计学意义(P<0.05),并且高表达CLEC9A的肝癌患者预后比低表达CLEC9A的肝癌患者较好,具有较低的临床分期,总体生存期[风险比(HR)=0.61,P<0.05]和疾病特异生存期(HR=0.54,P<0.05)均显著长于低表达CLEC9A的肝癌患者;CLEC9A的表达与免疫细胞浸润丰度正相关,高表达CLEC9A的肝癌患者CD8^(+)T细胞(28.310±3.855比17.328±2.573)和Th1细胞(5.470±1.548比1.261±0.521)浸润较低表达CLEC9A的肝癌患者显著(t=2.370、2.577,P<0.05)。结论CLEC9A可能通过调节肝癌的抗肿瘤免疫反应而参与肝癌的进展,有望成为肝癌诊治过程中预测患者预后的参考标准和新型治疗靶标。

Objective The goal of this study is to reveal the role of C-type lectin domain family 9A(CLEC9A)in liver cancer based on bioinformatic analysis.Methods CLEC9A expression was analyzed in the cancer genome atlas(TCGA)pan-cancer cohort that contained the RNA-seq data and clinical data.Overall survival and disease-specific survival were analyzed using the Kaplan-Meier method.Patients were also assessed for the correlation between the CLEC9A expression and clinicopathologic characteristics in liver cancer.The relationships between CLEC9A and infiltrating immune cells in liver cancer were performed by the gene set variation analysis(GSVA)and immunohistochemical method.Results Differential gene expression analysis based on the comparison between paired/non-paired pan-cancer and normal samples demonstrated that CLEC9A was significantly decreased in liver cancer[0.183(0.069-0.338)vs.0.343(0.242-0.515),0.187(0.076-0.405)vs.0.343(0.242-0.515),P<0.05].Patients with the higher levels of CLEC9A expression,and lower stage disease,had longer overall survival[hazard rate(HR)=0.61,P<0.05]and disease-specific survival(HR=0.54,P<0.05)in liver cancer.Notably,higher CLEC9A expression was also associated with a higher abundance of immune infiltrates in liver cancer,and in particular CD8^(+)T cells(28.310±3.855 vs.17.328±2.573,t=2.370,P<0.05)and Th1 cells(5.470±1.548 vs.1.261±0.521,t=2.577,P<0.05).Conclusion CLEC9A might represent a key factor that determines liver cancer development and progression via the modulations in the immune system and hold promise as a novel target for patient prognosis prediction and anticancer therapeutics.