弥漫性大B细胞淋巴瘤预后相关lncRNA分子筛选

Molecular screening of lncRNAs associated with prognosis of diffuse large B-cell lymphoma

[目的]用生信技术挖掘弥漫性大B细胞淋巴瘤(DLBCL)预后相关的长链非编码RNA(lncRNA),探究其靶基因潜在的生物功能及核心靶基因。[方法]使用TCGA数据库中弥漫大B细胞淋巴瘤患者的基因表达矩阵和临床数据,以及GTEx中正常组织的表达矩阵,利用Cox回归筛选弥漫性大B细胞淋巴瘤预后相关的lncRNA。在筛选表达及预后差异显著的lncRNA后,使用LncSEA数据库预测其靶基因,并通过R包clusterProfiler进行GO和KEGG富集分析。最后,用STRING构建靶基因蛋白互作网络(PPI),并使用cytoscape筛选核心互作蛋白。[结果]得到了30个与弥漫大B细胞淋巴瘤预后显著的风险因子,其中LINC01473和SEC24B-AS1在DLBCL的表达显著高于正常对照组且预后显著;LINC01473和SEC24B-AS1的靶基因GO主要富集于转录调节复合物、DNA结合转录因子结合等生物过程;Cytoscape筛选出LINC01473和SEC24B-AS1的10个关键靶基因,包括EP300、MYC、TP53、JUN、HDAC1、SMAD4、ESR1、FOS、CEBPA和AR。[结论]LINC01473和SEC24B-AS1是弥漫性大B细胞淋巴瘤中高表达且预后显著的lncRNA,其靶基因调控通路及核心关键靶基因揭示了该疾病的生物学过程,为早期诊断治疗提供了生物标志物。

[Objective]To explore the potential biological functions and core target genes of long non-coding RNA(lncRNA)related to prognosis of diffuse large B-cell lymphoma(DLBCL)by bioinformatics.[Method] Using the gene expression matrix and clinical data of patients with diffuse large B-cell lymphoma in the TCGA database and the expression matrix of normal tissues in GTEx,Cox regression was used to screen lncrnas associated with the prognosis of diffuse large B-cell lymphoma.After screening IncRNAs with significant differences in expression and prognosis,LncSEA database was used to predict their target genes,and GO and KEGG enrichment analysis was performed by R-package clusterProfiler.Finally,STRING was used to construct the target gene protein interaction network(PPI)and cytoscape was used to screen the core interacting proteins.[Result]A total of 30 risk factors were found to be associated with diffuse large B-cell lymphoma.The expression of LINCO1473 and SEC24B-ASI in DLBCL was significantly higher than that in normal control group,and the prognosis was significant.The target genes GO of LINCO1473 and SEC24B-ASI are mainly enriched in the transcriptional regulatory complex,DNA-binding transcription factor binding and other biological processes.Cytoscape selected 10 key target genes of LINCO1473 and SEC24B-ASI,including EP300,MYC,TP53,JUN,HDAC1,SMAD4,ESR1,FOS,CEBPA and AR.[Conclusion ] LINCO1473 and SEC24B-ASI are highly expressed lncrnas with significant prognosis in DLBCL.Their target gene regulatory pathways and core key target genes reveal the biological process of this disease and provide biomarkers for early diagnosis and treatment.