视神经病变诱导反应蛋白在多发性骨髓瘤中的表达及临床意义

Expression of optineurin in multiple myeloma and its clinical significance

目的研究视神经病变诱导反应蛋白(optineurin,OPTN)基因在多发性骨髓瘤(multiple myeloma,MM)中的表达情况,探讨OPTN基因参与MM发生发展的机制和临床价值。方法利用3个基因表达数据库(gene expression omnibus,GEO)数据集(GSE6477、GSE136324和GSE24080),分析OPTN在MM中的表达;通过收集MM患者临床骨髓标本,利用qRT-PCR实验进一步验证OPTN在MM患者中的表达情况。使用Kaplan-Meier生存曲线、受试者工作特征(receiver operating characteristic,ROC)曲线分析OPTN在MM预后和诊断中的价值。同时利用癌症基因组图谱(the Cancer Genome Atlas,TCGA)数据库下载MM转录组数据,根据OPTN mRNA表达水平中位数界,将MM患者分为OPTN高、低表达组,用R语言limma包筛选差异表达基因后,对差异基因进行富集分析(gene set enrichment analysis,GSEA)从而挖掘OPTN在MM中的潜在临床意义及其可能参与的分子机制。结果OPTN在MM组织中表达显著低于正常组织(P<0.05);OPTN表达变化与MM患者的国际分期体系(International Staging System,ISS)显著相关(P<0.05);ROC结果显示OPTN表达变化可区分正常人和MM患者。生存分析显示OPTN低表达患者总生存率(overall survival,OS)显著低于高表达患者(P<0.05)。GO、KEGG和GSEA富集分析结果表明,OPTN可能通过调控NOD样受体、NF-κB、TNF及RAS/MAPK等通路进而影响细胞凋亡、自噬及调节细胞免疫反应等参与MM的进程。结论OPTN在多发性骨髓瘤中低表达,与患者预后不良相关,可能作为MM诊断及治疗的重要潜在生物标志物。

Objective To investigate the expression of optineurin(OPTN) in multiple myeloma(MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM.Methods In this study,three gene expression omnibus(GEO) data sets were used to analyze the expression level of OPTN in MM.Clinical bone marrow samples of MM patients were collected.qRT-PCR was used to further verify the expression of OPTN in MM patients.The Kaplan-Meier survival curve and receiver operating characteristic(ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM.At the same time,MM transcriptome data were downloaded from the Cancer Genome Atlas(TCGA) database.According to the median boundary of OPTN mRNA expression level,the MM patients were divided into OPTN high-and low-expression groups.In order to investigate the possible molecular mechanisms of OPTN in MM,gene set enrichment analysis(GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language.Results The expression level of OPTN was significantly lower in MM tissues than in normal tissues(P<0.05).OPTN expression level was significantly correlated with International Staging System(ISS) in MM patients(P<0.05).ROC results showed that the expression level of OPTN could distinguish between normal and MM patients.Survival analysis showed that the overall survival(OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression(P<0.05).GO,KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy,and regulate cellular immune response by regulating Nod-like receptors,NF-κB,TNF and RAS/MAPK pathways.Conclusion Low expression of OPTN in MM is associated with poor prognosis of patients,and thus may be an important potential biomarker for the diagnosis and treatment of MM.