摘要
目的探讨m^(6)A RNA甲基化调控因子在甲状腺癌中的作用。方法在TCGA数据库中获取甲状腺癌样本510例和正常对照样本58例的RNA-seq转录组数据及相应甲状腺癌患者的临床病理资料。比较13种m^(6)A RNA甲基化调控因子在甲状腺癌和正常甲状腺组织中的表达水平。基于一致性聚类分析将甲状腺癌组织分为2个聚类,并比较其总体生存率和临床病理特征的差异。进一步利用单因素COX回归分析筛选出与甲状腺癌患者预后相关因子,并将其纳入LASSO回归分析,构建患者的风险特征模型,进而评估风险特征模型的预测价值。结果除YTHDF2外,余12个m^(6)A RNA甲基化调控因子在甲状腺癌组织中的表达与正常甲状腺组织比较差异均有统计学意义。在一致性聚类分析中,聚类2的总体生存率明显低于聚类1。基于3个高风险调控因子(RBM15、KIAA1429和FTO)构建风险特征模型并用于风险评分计算。高危组和低危组的总体生存率,RBM15、KIAA1429、FTO表达和T状态比较差异有统计学意义(P<0.05)。ROC曲线显示,风险评分可以预测甲状腺癌患者的5年生存率(AUC=0.717),多因素Cox回归分析表明,风险评分是甲状腺癌的独立预后指标(P=0.001)。结论m^(6)A RNA甲基化调控因子影响甲状腺癌的进展,其中RBM15、KIAA1429和FTO可作为临床预后标志物,在治疗决策中具有潜在价值。
Objective The role of m^(6)A RNA methylation modulators in thyroid carcinoma was investigated by analyzing RNA-seq transcriptome results and corresponding clinical data of 568 thyroid carcinoma samples from The Cancer Genome Atlas(TCGA)database.Methods The expression levels of 13 major m^(6)A RNA methylation modulators between thyroid carcinoma and normal thyroid tissues were compared.Based on consensus clustering of these modulators,carcinoma tissues were divided into two clusters,whose overall survival(OS)and clinicopathological features are compared.The least absolute shrinkage and selection operator(LASSO)Cox regression were used to set up risk signature for risk score calculation and the predictive value of risk score was further evaluated.Results The expression of modulators in thyroid carcinoma was significantly different from that in normal thyroid tissues except for YTHDF2.In consensus clustering analysis,the OS of cluster 2 was significantly poorer than cluster 1.Three high OR modulators(RBM15,KIAA1429 and FTO)were identified for risk signature and used for risk score calculation.There were significant differences in survival and clinicopathological features analysis between the high vs.low-risk group(P<0.05).The ROC curve indicated that the risk score can predict survival rates of thyroid carcinoma patients(AUC=0.717).Multivariate Cox regression analysis showed that risk score was an independent prognostic marker of thyroid carcinoma(P=0.001).Conclusion The m^(6)A RNA methylation modulators influence the progression of thyroid carcinoma,among which RBM15,KIAA1429 and FTO can be clinical prognostic markers and have potential value in treatment decisions.
作者
黄甜甜
段碧晗
叶迎春
王硕
高凌
Huang Tiantian;Duan Bihan;Ye Yingchun;Wang Shuo;Gao Ling(Department of Endocrinology &Metabolism, Renmin Hospital of Wuhan University, Hubei Province,Wuhan 430060, China)
出处
《疑难病杂志》
CAS
2021年第5期481-487,共7页
Chinese Journal of Difficult and Complicated Cases
基金
国家自然科学基金资助项目(81571376)。
