Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling
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DOI:
10.1038/modpathol.2012.220
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发表时间:
2013-07-01
期刊:
影响因子:
7.5
通讯作者:
Mollejo, Manuela
Mollejo, Manuela
中科院分区:
医学1区
文献类型:
--
作者:
Arribas, Alberto J.;Gomez-Abad, Cristina;Mollejo, Manuela

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脾边缘带淋巴瘤是一种小b细胞肿瘤,其分子发病机制仍基本未知,其与其他小b细胞淋巴瘤的区分因缺乏特异性标记物而受到阻碍。我们分析了31例脾边缘区淋巴瘤的基因表达和miRNA谱。其中反应性淋巴样增生7例,慢性淋巴细胞白血病浸润10例,滤泡性淋巴瘤12例,套细胞淋巴瘤浸润6例,淋巴结边缘区淋巴瘤浸润15例。结果通过qRT-PCR在77例石蜡包埋的脾边缘区淋巴瘤的独立序列中得到验证。脾边缘区淋巴瘤miRNA特征有51个miRNA表达失调。高表达mirna为miR-155、miR-21、miR-34a、miR-193b和miR-100,低表达mirna为miR-377、miR-27b、miR-145、miR-376a和miR-424。与反应性淋巴样组织和其他b细胞淋巴瘤相比,位于14q32-31的MiRNAs在脾边缘区淋巴瘤中表达不足。最后,将基因表达数据与miRNA谱相结合,以确定基因与解除调控的miRNA之间的功能关系。我们的研究揭示了在脾边缘区淋巴瘤中失调的mirna,并确定了脾边缘区淋巴瘤的新候选诊断分子。
Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.