肝癌m^(6)A RNA甲基化调控因子风险预测模型的构建及其临床意义

Construction of liver cancer N^(6)-methyladenosine RNA methylation regulators risk prediction models and its clinical significance

目的建立肝癌N^(6)-甲基腺嘌呤(N^(6)-methyladenosine,m^(6)A)RNA甲基修饰调控因子风险预测模型,并探讨其临床意义。方法通过收集癌症基因组图谱(TCGA)和国际癌症基因组联盟(ICGC)数据库中肝癌病人mRNA表达谱及临床资料相关数据,分析肝癌中18种m^(6)A调控因子在肿瘤组织与正常组织中的表达差异;使用单因素Cox比例风险回归分析方法筛选预后相关m^(6)A调控因子并利用LASSO算法建立风险预测模型。结果与正常组织相比,肝癌组织中18种m^(6)A调控因子中除METTL14外,其余表达水平差异均有统计学意义(P<0.05);筛选^(6)个调控因子(YTHDF2,LRPPRC,YTHDF1,METTL3,KIAA1429,ZC3H13)建立风险预测模型,发现其与肝癌病人临床病理特征及预后密切相关。结论m^(6)A调控因子风险预测模型与肝癌病人临床病理特征及预后密切相关,有望用于指导肝癌的临床治疗。

Objective To construct a risk prediction model of liver cancer N^(6)-methyladenosine RNA methylation regulators and discuss its clinical significance.Methods The mRNA expression profile and clinical data of liver cancer patients were collected from the databases of TCGA and ICGC and the differential expressions of 18 kinds of m^(6)A regulator between tumor tissues and normal tissues were analyzed.Univariate Cox regression analysis was performed for selecting the prognostic related m^(6)A regulators and LASSO algorithm utilized for constructing a risk prediction model.Results Compared to normal tissues,the expression levels of 18 kinds of m^(6)A regulators except for METTL14 spiked markedly in liver cancer tissues(P<0.05).The prognosis risk model was constructed by selecting six m^(6)A regulators of YTHDF2,LRPPRC,YTHDF1,METTL3,KIAA1429 and ZC3H13.These m^(6)A regulators were closely correlated with the clinicopathological characteristics and prognosis of liver cancer patients.Conclusion The risk prediction model of m^(6)A regulatory factors is closely correlated with the clinicopathological characteristics and prognosis of patients with liver cancer.And it is expected to guide the clinical treatment of liver cancer.