儿童骨肉瘤中TP53突变与免疫分子基因表达的相关性分析  

Correlation between TP53 mutation and immune response in childhood osteosarcoma

作　　者：郭梅[1] 李渝华[1] 荆安龙 GUO Mei;LI Yuhua;JING Anlong(Department of Pediatrics,Hechuan People's Hospital,Chongqing 401520,China.;Department of Orthopedics,Hechuan People's Hospital,Chongqing 401520,China.)

机构地区：[1]重庆市合川区人民医院儿科,重庆401520 [2]重庆市合川区人民医院骨科,重庆401520

出　　处：《现代肿瘤医学》2022年第15期2837-2841,共5页Journal of Modern Oncology

摘　　要：目的:筛选儿童骨肉瘤中突变基因,并研究其表达与免疫反应的关系。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载全部234例骨肉瘤病例数据集,从基因表达数据库(Gene Expression Omnibus,GEO)下载数据集GSE36001(19个肿瘤样本和6个正常样品)和GSE39055(37例肿瘤样本和12个正常样本),包括基因突变数据、转录组数据和临床数据,进行生物信息学分析。收集11例骨肉瘤手术样本,实时荧光定量PCR验证临床样本中基因表达。结果:67.09%的骨肉瘤患者存在突变,其中错义突变、单核苷酸变异和C>T突变较多,突变基因排在前10位的分别为TP53、TTN、ATRX、MUC16、RB1、PCLO、RYR2、CSMD1、USH2A、MUC17。在数据集GSE36001和GSE39055中,骨肉瘤组织中TP53均过表达(P<0.0001)。在11例病例样本中,骨肉瘤组织中TP53表达高于正常组织(P=0.002)。TCGA中,TP53突变型表达高于TP53野生型(P=0.015)。在11例病例样本中,TP53突变型表达高于TP53野生型(P=0.038)。TCGA中,突变型TP53表达与DNA甲基化呈显著负相关(P=0.003)。在TP53突变的骨肉瘤样本中,B细胞、T细胞CD8+相关的免疫应答显著下调,CD274和CTLA4显著高表达(P<0.05)。结论:TP53突变与骨肉瘤的发生及免疫反应密切相关,有望成为骨肉瘤诊断和治疗的作用靶点。Objective:To screen mutant genes in osteosarcoma and study the relationship between their expression and immune response.Methods:Download the dataset of all 234 cases of osteosarcoma from The Cancer Genome Atlas(TCGA),and download the dataset GSE36001(19 tumor samples and 6 normal samples)and GSE39055(37 tumor samples and 12 normal samples)from the Gene Expression Omnibus(GEO),including gene mutation data,transcriptome data and clinical data,for bioinformatics analysis.Collect 11 surgical samples of osteosarcoma,and verify gene expression in clinical samples by RT-qPCR.Results:67.09%of patients with osteosarcoma had mutations,including missense mutations,single nucleotide mutations and C>T mutations.The top 10 mutant genes were TP53,TTN,ATRX,MUC16,RB1,PCLO,RYR2,CSMD1,USH2A and MUC17.In the data sets GSE36001 and GSE39055,TP53 was overexpressed in osteosarcoma tissues(P<0.0001).In 11 cases,the expression of TP53 in osteosarcoma tissue was higher than that in normal tissue(P=0.002).In the TCGA database,the expression of TP53 mutant type was higher than that of TP53 wild type(P=0.015).In 11 case samples,the expression of TP53 mutant type was higher than that of TP53 wild type(P=0.038).In TCGA,the expression of mutant TP53 was significantly negatively correlated with DNA methylation(P=0.003).In TP53-mutated osteosarcoma samples,B cells and T cells CD8+related immune responses were significantly down-regulated,and CD274 and CTLA4 were significantly overexpressed(P<0.05).Conclusion:TP53 mutation is closely related to the occurrence and immune response of osteosarcoma,and is expected to become a target for the diagnosis and treatment of osteosarcoma.

关 键 词：骨肉瘤 TP53 突变 免疫评分 免疫检查点 

分 类 号：R738.1[医药卫生—肿瘤]