摘要
目的筛选出弥漫大B细胞淋巴瘤(DLBCL)预后相关基因,明确预后相关基因表达水平与DLBCL患者预后及肿瘤浸润性免疫细胞(TICs)比例的关系,为DLBCL治疗提供新的靶点。方法从GEO中获取GSE56315、GSE12453和GSE87371芯片数据,用R的“limma”包筛选出DLBCL预后相关基因。将GSE87371数据集中的预后相关基因根据表达量中位值分为高、低表达组,从R语言的“survival”包中提取高、低表达组5年OS率及95%CI,然后利用COX风险回归模型分析预后相关基因与预后的相关性,使用R语言的“for”循环分析预后不良相关基因与DLB-CL患者年龄、性别、临床分期等临床参数的关系。通过GSEA富集分析DLBCL预后相关基因在DLBCL中的相关信号通路。最后利用CIBERSORT算法计算DLBCL组织中TICs的比例,并分析预后相关基因表达水平与TICs比例的关系。结果对GSE12353及GSE56315进行合并后的MERGE基因集进行筛选后获得DLBCL组织与正常组织的差异表达基因445个(上调基因301个,下调基因143个),从GSE87371数据集获得DLBCL预后相关基因57个(负相关17个,正相关40个),将上调的301个差异表达基因与负相关的17个基因取交集,获得膜连蛋白1(ANXA1),即为DLBCL预后相关基因。ANXA1高表达组5年OS率3.56%,95%CI 1.17%~10.7%,低表达组5年OS率17.49%,95%CI为11.8%~29.9%,ANXA1高表达组DLBCL患者5年OS率低于低表达组(P<0.001);ANXA1为DLBCL独立预后影响因子(P<0.05);ANXA1表达水平与患者临床参数无相关性(P>0.05)。ANXA1在趋化因子信号通路、MAPK信号通路、ECM受体相互作用、JAK-STAT信号通路等通路上富集。DLBCL组织中T细胞和巨噬细胞比例较大,分别为49%、31%;ANXA1表达水平与巨噬细胞M2、浆细胞、活性CD4+记忆T细胞、CD8+T细胞、γδT细胞比例正相关(P均<0.001)。结论DLBCL预后相关基因为ANXA1,ANXA1表达水平高与DLBCL患者预后不良及肿瘤免疫浸润细胞比例相关,富集的信号通路主要有�
Objective To screen out the prognosis-related genes in diffuse large B-cell lymphoma(DLBCL)and to confirm the relationship between the expression of prognosis-related genes and patients’survival and the proportion of tu-mour-infiltrating immune cells(TICs)to provide new targets for the treatment and prognosis of DLBCL.Methods GSE56315,GSE12453 and GSE87371 microarray data were obtained from GEO,and DLBCL prognosis-associated genes were screened using the R"limma"package.Prognosis-related genes were analyzed for survival,independent prognosis,and correlation between prognosis-related gene expression levels and clinical parameters.The target genes in the GSE87371 datasets were categorised into high and low expression groups according to their median expression values,and the 5-year OS rates and 95%CIs of the high and low expression groups were extracted from the"survival"package in R.The correlation between the target genes and prognosis was then analyzed using COX risk regression models.Finally,"for loop"was used to analyse the relationship between the target gene and clinical parameters such as age,gender and clinical stage of DLBCL patients.The functional pathways of DLBCL prognosis-related genes in DLBCL were analyzed by GSEA enrichment.Finally,the CIBERSORT algorithm was used to calculate the proportion of TICs in DLBCL tis-sues and to analyse the relationship between the expression levels of prognosis-related genes and the proportion of TICs.Results The merged MERGE gene set of GSE12353 and GSE56315 was screened.We obtained 445(301 up-regulated genes and 143 down-regulated genes)differentially expressed genes;57 prognosis-related genes(17 negatively and 40 pos-itively correlated)were obtained from the GSE87371 dataset,and the 301 differentially up-regulated genes and the 17 neg-atively correlated genes were intersected to obtain membrane linked protein 1(ANXA1),which was a DLBCL prognosisassociated gene.Survival analysis suggested a 5-year OS rate of 3.56%(95%CI 1.17%-10.7%)in the high ANXA1 ex-pression gro
作者
郭佳丽
潘晨华
李依
刘晓倩
蒋慧
常伟
GUO Jiali;PAN Chenhua;LI Yi;LIU Xiaoqian;JIANG Hui;CHANG Wei(School of Medicine,Wuhan University of Science and Technology,Wuhan 430080,China;不详)
出处
《山东医药》
CAS
2023年第3期33-36,共4页
Shandong Medical Journal
基金
湖北省卫生健康委联合基金项目(WJ2018H0113)
武汉市卫生计生委医学科研项目(WX21C23)
武汉市卫生计生委医学科研项目(WX18C32)。
