Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis
Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis
复制标题
套细胞淋巴瘤的全基因组 miRNA 分析揭示了一个预后不良的独特亚组。
DOI：
10.1182/blood-2011-07-370122
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发表时间：
2012-05-24
期刊：
影响因子：
20.3
通讯作者：
Chan, Wing C.
中科院分区：
文献类型：
--
作者：
Iqbal, Javeed;Shen, Yulei;Chan, Wing C.
MiRNA失控与套细胞淋巴瘤(MCL)的发病有关。应用高通量实时定量聚合酶链式反应技术，对30例细胞周期蛋白D1阳性的MCL和7例细胞周期蛋白D1阴性的MCL进行miRNA分析，并与小淋巴细胞性白血病/淋巴瘤(n=12)、侵袭性B细胞淋巴瘤(n=138)、正常B细胞亚群和基质细胞进行比较。我们鉴定了一个19-miRNA分类器，它包括6个上调的miRNA和13个下调的miRNA，能够将MCL与其他侵袭性淋巴瘤区分开来。一些上调的miRNAs在幼稚的B细胞中高表达。这种miRNA分类器在福尔马林固定的石蜡包埋组织中显示出一致的结果，并能够将Cyclin D1阴性的MCL与其他淋巴瘤区分开来。26-miRNA分类器可以区分MCL和小淋巴细胞性白血病/淋巴瘤，MCL中以23个上调的miRNAs为主。多顺反子miR17-92及其近亲miR-106a-363和miR-106b-25的miRNAs在MCL患者的非监督系统中呈高表达，并伴有高增殖基因特征。其他簇表现为基质相关miRNAs的丰富，并且基质相关基因的表达也较高。我们在本研究中的临床结果分析表明，miRNAs可以作为预后指标。
miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNA classifier showed consistent results in formalin-fixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.