儿童Ph+及Ph-like急性T淋巴细胞白血病二代测序分析  

Second-generation Sequencing Analysis of Ph and Ph-like Childhood T-cell Acute Lymphoblastic Leukemia

作　　者：廖欣[1,2] 邹品力 沈亚莉[1,2] 郭玉霞 宋林[2,3] 肖剑文 LIAO Xin;ZOU Pin-Li;SHEN Ya-Li;GUO Yu-Xia;SONG Lin;XIAO Jian-Wen(Department of Hematology and Oncology,Children's Hospital of Chongqing Medical University;National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Pediatrics;Department of Pharmacy,Children's Hospital of Chongqing Medical University,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院血液肿瘤科 [2]国家儿童健康与疾病临床医学研究中心,儿童发育疾病研究教育部重点实验室,儿科学重庆市重点实验室 [3]重庆医科大学附属儿童医院药学部,重庆400014

出　　处：《中国实验血液学杂志》2021年第4期1101-1108,共8页Journal of Experimental Hematology

摘　　要：目的:利用生物信息学方法筛选费城染色体阳性/费城染色体样急性T淋巴细胞白血病(Ph^(+)/Ph-like TALL)核心基因,并分析其核心子网络,探讨Ph^(+)/Ph-like T-ALL发生发展过程中的调控机制并寻找可能用于临床诊疗的分子靶点。方法:收集重庆医科大学附属儿童医院Ph^(+)/Ph-like T-ALL患儿WES/RNA-seq检查结果,同时从GEO数据库中下载符合要求的基因数据,运用GRO2R在线差异表达基因筛选程序筛选差异性表达基因,并对差异表达基因进行GO功能富集分析和KEGG通路分析,同时使用STRING数据库,利用Cytoscape软件构建蛋白质相互作用网络,筛选出hub gene及核心子网络。结果:Ph^(+)/Ph-like T-ALL共找出84个差异表达基因,Ph^(+)ALL共找出249个差异表达基因,T-ALL共找出175个差异表达基因。综合GO功能富集、KEGG通路富集分析及蛋白相互作用网络结果,筛选出RPA1、POLD1、POLE、SOCS1为hub gene。DNA损伤修复及JAK/STAT信号转导通路为筛选到的主要功能子网络。结论:Ph^(+)/Ph-like T-ALL患儿体内存在明显的DNA损伤修复通路异常,RPA1、POLD1、POLE可能是Ph^(+)/Ph-like T-ALL发生、发展的重要相关生物标志,这可以为进一步研究提供依据。Objective: To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia( Ph ^(+)/Ph like T-ALL) using bioinformatics methods,and analyze the core sub-networks for exploration of the development process of Ph ^(+)/Ph like T-ALL,so as to find the molecular targets that may be used in clinical diagnosis and treatment. Methods: The WES/RNA-seq examination results of Ph ^(+)/Ph-like T-ALL children had be collected in our hospital,the genetic data that met the requirements had be downloaded from GEO database,then GRO2 R online differentially expressed gene screening program was used to screen differentially expressed genes,finally,GO function enrichment analysis and KEGG pathway enrichment analysis were performed to compare differentially expressed genes. At the same time,STRING database and Cytoscape software were used to build protein interaction network and screen hub genes and core sub-networks. Results: For Ph ^(+)/Ph like T-ALL,a total of 84 differentially expressed genes had been found,for Ph ^(+) ALL a total of 249 differentially expressed genes,and for T-ALL a total of 175 differentially expressed genes. Based on the results of GO function enrichment,KEGG pathway enrichment analysis and protein interaction network,RPA1,POLD1,POLE and SOCS1 were selected as hub genes. DNA damage repair and JAK/STAT signal transduction pathway were the main functional sub-networks. Conclusion: There are obviously abnormal DNA damage repair pathways in children with Ph ^(+)/Ph like T-ALL. RPA1,POLD1 and POLE may be important relevant biomarkers for the occurrence and development of Ph ^(+)/Ph like T-ALL,which can provide a basis for further research.

关 键 词：费城染色体 费城染色体样急性T淋巴细胞白血病 二代测序 基因富集分析 

分 类 号：R733.71[医药卫生—肿瘤]