摘要目的 通过分析非特指型外周T细胞淋巴瘤(PTCL-NOS)肿瘤组织中microRNA(miRNA)的表达情况,探索其分子改变特征.方法 收集21例PTCL-NOS,发生于淋巴结内15例,淋巴结外6例；炎性反应增生性淋巴结组织13例；其中6例PTCL-NOS和3例炎性反应增生性淋巴结的石蜡包埋组织,应用TaqMan低密度芯片分析754种miRNA的表达差异；采用Targetscan与miRanda软件对显著差异的miRNA进行靶基因预测分析,应用生物信息学方法对靶基因进行显著的基因本体(GO)和信号通路分析.应用即时定量聚合酶链反应(qRT-PCR)进一步验证3种miRNA(miR-511、miR-1291、miR-572)在15例PTCL-NOS与10例炎性反应增生性淋巴结中的表达情况.结果 芯片检测发现7种miRNA(miR-886-3p、miR-511、miR-1291、miR-572、miR-27a-3p、miR-25-3p、miR-886-5p)在PTCL-NOS中表达上调,而miR-182-5p表达下调(P＜0.05).预测靶基因显著性GO有63个、信号通路61条.3种miRNA的qRT-PCR结果与芯片分析miRNA表达趋势相同,其中miR-572和miR-1291在PTCL-NOS中表达上调,差异具有统计学意义(P＜0.05).结论 这8种miRNA在PTCL-NOS中表达异常,可能参与该肿瘤发生发展的分子调控；其中涉及多种靶基因与复杂的信号通路.

abstractsObjective To study the expression profile of microRNAs (miRNAs) in peripheral T cell lymphoma,not otherwise specified (PTCL-NOS) and to explore the underlying molecular characteristics.Methods Twenty-one cases of PTCL-NOS were enrolled into the study.The tumor presented either as nodal (15/21) or extranodal (6/21) disease.TaqMan low density array was used to assess the expression level of 754 miRNAs in six cases of PTCL-NOS and three control cases of reactive lymphoid hyperplasia.Prediction of target genes for significant and differential expression of miRNAs was carried out using Targetscan and miRanda software.Bioinformatics tools were employed for GO-Analysis and Pathway-Analysis of target genes.The expression patterns of the three miRNAs were further analyzed in the remaining 15 cases of PTCL-NOS and 10 cases of reactive lymphoid hyperplasia,using single tube Taqman miRNA assays.Results Eight miRNAs showed statistically significant difference in expression between PTCL-NOS and reactive lymphoid hyperplasia.miR-886-3p,miR-511,miR-1291,miR-572,miR-27a-3p,miR-25-3p and miR-886-5p were significantly overexpressed in PTCL-NOS while miR-182-5p was significantly underexpressed (P ＜ 0.05).Target gene prediction showed that 1646 candidate genes involved in the pathogenesis and progression of PTCL-NOS.Further GO and Pathway-Analyses found that these genes significantly focused on 63 GO terms and 61 pathways.The results of three miRNA qRT-PCR confirmed that miR-572 and miR-1291 expression in PTCL-NOS had statistical significance.Conclusions Eight miRNAs are aberrantly expressed in PTCL-NOS,which may be involved in molecular regulation during the development of PTCL-NOS.The underlying mechanism is also related to a number of target genes and signaling pathways.