未另行分类的外周T细胞淋巴瘤中microRNA失调的致病与诊断意义
Pathogenetic and diagnostic significance of microRNA deregulation in peripheral T-cell lymphoma not otherwise specified
原文发布日期:2014-11-07
DOI: 10.1038/bcj.2014.78
类型: Original Article
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Peripheral T-cell lymphomas not otherwise specified (PTCLs/NOS) are rare and aggressive tumours whose molecular pathogenesis and diagnosis are still challenging. The microRNA (miRNA) profile of 23 PTCLs/NOS was generated and compared with that of normal T-lymphocytes (CD4+, CD8+, naive, activated). The differentially expressed miRNA signature was compared with the gene expression profile (GEP) of the same neoplasms. The obtained gene patterns were tested in an independent cohort of PTCLs/NOS. The miRNA profile of PTCLs/NOS then was compared with that of 10 angioimmunoblastic T-cell lymphomas (AITLs), 6 anaplastic large-cell lymphomas (ALCLs)/ALK+ and 6 ALCLs/ALK−. Differentially expressed miRNAs were validated in an independent set of 20 PTCLs/NOS, 20 AITLs, 19 ALCLs/ALK− and 15 ALCLs/ALK+. Two hundred and thirty-six miRNAs were found to differentiate PTCLs/NOS from activated T-lymphocytes. To assess which miRNAs impacted on GEP, a multistep analysis was performed, which identified all miRNAs inversely correlated to different potential target genes. One of the most discriminant miRNAs was selected and its expression was found to affect the global GEP of the tumours. Moreover, two sets of miRNAs were identified distinguishing PTCL/NOS from AITL and ALCL/ALK−, respectively. The diagnostic accuracy of this tool was very high (83.54%) and its prognostic value validated.
非特指型外周T细胞淋巴瘤(PTCLs/NOS)是一种罕见且侵袭性强的肿瘤,其分子发病机制与诊断仍面临挑战。研究对23例PTCLs/NOS进行了microRNA(miRNA)谱分析,并与正常T淋巴细胞(CD4+、CD8+、初始态、活化态)进行对比。将差异表达的miRNA特征与同一批肿瘤的基因表达谱(GEP)进行关联分析,并在独立队列的PTCLs/NOS中验证所得基因模式。进一步将PTCLs/NOS的miRNA谱与10例血管免疫母细胞性T细胞淋巴瘤(AITL)、6例间变性大细胞淋巴瘤(ALCL)/ALK+及6例ALCL/ALK−进行比较。差异表达miRNA在独立样本集(20例PTCLs/NOS、20例AITL、19例ALCL/ALK−和15例ALCL/ALK+)中得到验证。研究共发现236个miRNA可区分PTCLs/NOS与活化T淋巴细胞。为评估miRNA对GEP的影响,通过多步骤分析鉴定出所有与不同潜在靶基因呈负相关的miRNA。选取最具判别力的miRNA之一,发现其表达影响肿瘤整体GEP。此外,分别确定了两组可区分PTCL/NOS与AITL、以及PTCL/NOS与ALCL/ALK−的miRNA组合。该工具的诊断准确率极高(83.54%),其预后价值也得到验证。
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