RNA甲基化修饰N6-甲基腺苷在黑色素瘤预后及免疫微环境中的作用  

Effect of RNA methylation modification N~6-methyladenosine in the prognosis and immune microenvironment of melanoma

作　　者：董政 谭谦[1] DONG Zheng;TAN Qian(Department of Burn and Plastic Surgery,Drum Tower Hospital Affiliated to Medical School of Nanjing University,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院整形烧伤科,江苏南京210008

出　　处：《中国美容整形外科杂志》2022年第12期729-733,I0009,共6页Chinese Journal of Aesthetic and Plastic Surgery

摘　　要：目的黑色素瘤中构建基于m^(6)A甲基化调控因子的风险模型,以探究m^(6)A甲基化调控因子在黑色素瘤中的预后和免疫治疗价值。方法自2022年1—2月,南京大学医学院附属鼓楼医院整形烧伤科从癌症基因组图谱(the cancer genome atlas,TCGA)和基因型组织表达(genotype tissue expression,GTEx)数据库中收集470例黑色素瘤样本的基因表达数据和相应的临床信息以及1809例正常对照样本的序列数据。独立t检验分析20个m^(6)A甲基化调控因子在肿瘤和正常组织的差异表达。一致性聚类分析基于m^(6)A甲基化调控因子将黑色素瘤患者分为两个聚类,CIBERSORT分析比较两个聚类患者群体免疫浸润水平。通过Cox回归分析筛选与黑色素瘤预后显著相关的基因。Lasso回归分析用来构建在黑色素瘤中的风险预测模型。结果黑色素瘤样本与正常样本在不同m^(6)A甲基化调控因子间差异具有统计学意义,其中ZC3H13、YTHDF3、IGF2BP2、IGF2BP3在黑色素瘤中明显高表达(P<0.05)。聚类分析和CIBERSORT分析显示,集群1与集群2存在免疫浸润差异。基于Lasso回归分析筛选出RBM15B和WTAP作为m^(6)A相关的预后模型,高风险组患者生存期明显缩短(P=0.00179)。多因素Cox回归分析显示,RBM15B是黑色素瘤预后的独立预测因素,结合CIBERSORT分析显示,RBM15B高表达与浸润性免疫细胞具有相关性。结论m^(6)A甲基化调控因子在黑色素瘤中可以提示免疫浸润情况。基于黑色素瘤中关键m^(6)A甲基化调控因子所构建的预后风险模型具有较好的预测能力。RBM15B可能为黑色素瘤潜在风险因素和免疫浸润潜在相关m^(6)A调控因子。这项研究为对m^(6)A调控因子的表观遗传学理解和黑色素瘤的新治疗策略提供了新的见解。Objective To construct a risk model based on m^(6)A methylation regulators in melanoma.To explore the value of m^(6)A methylation regulators in the prognosis and immunotherapy of melanoma.Methods From January 2022 to February,the data of gene expression and corresponding clinical information of 470 melanoma samples as well as sequence data of 1809 normal control samples were collected from The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.The differential expressions of 20m^(6)A methylation regulators between melanoma and normal tissue was analyzed by independent t test.Based on m^(6)A methylation regulators,the melanoma patients were divided into two clusters by consensus clustering.The immune infiltration of two clusters was estimated by CIBERSORT.Genes significantly associated with melanoma prognosis was screened by Cox regression analysis.The risk model in melanoma was constructed by Lasso Cox regression analysis.Results There were statistical significance in difference of various m^(6)A methylation regulators between melanoma samples and normal samples.The ZC3H13,YTHDF3,IGF2BP2 and IGF2BP3 were remarkably up-regulated in melanoma(P<0.05).The clustering analysis and CIBERSORT analysis showed that there were differences in immune infiltration between clusters 1 and 2.Based on Lasso Cox regression analysis,RBM15B and WTAP were screened as prognostic model associated with m^(6)A,patients in the high-risk group had a worse prognosis(P=0.00179).Multivariate Cox regression analysis showed that RBM15B was an independent prognostic factor of melanoma.CIBERSORT analysis showed that high expression of RBM15B was associated with immune infiltration.Conclusion The m^(6)A methylation regulators can indicate immune infiltration in melanoma.The prognostic risk model constructed according to crucial m^(6)A methylation regulators in melanoma has good predictive ability.RBM15B may be a potential risk factor of melanoma and potential relevant m^(6)A regulators of immune infiltration.This study provi

关 键 词：黑色素瘤 m6A甲基化调控因子 RBM15B 生物信息学分析 

分 类 号：R739.5[医药卫生—肿瘤]