Cascione Luciano, Giudice Luca, Ferraresso Serena, Marconato Laura, Giannuzzi Diana, Napoli Sara, Bertoni Francesco, Giugno Rosalba, Aresu Luca
Institute of Oncology Research, Universita' della Svizzera Italiana, 6500 Bellinzona, Switzerland.
Swiss Institute of Bioinformatics, 1000 Lausanne, Switzerland.
Noncoding RNA. 2019 Sep 19;5(3):47. doi: 10.3390/ncrna5030047.
Diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) are the most common B-cell lymphomas (BCL) in dogs. Recent investigations have demonstrated overlaps of these histotypes with the human counterparts, including clinical presentation, biologic behavior, tumor genetics, and treatment response. The molecular mechanisms that underlie canine BCL are still unknown and new studies to improve diagnosis, therapy, and the utilization of canine species as spontaneous animal tumor models are undeniably needed. Recent work using human DLBCL transcriptomes has suggested that long non-coding RNAs (lncRNAs) play a key role in lymphoma pathogenesis and pinpointed a restricted number of lncRNAs as potential targets for further studies.
To expand the knowledge of non-coding molecules involved in canine BCL, we used transcriptomes obtained from a cohort of 62 dogs with newly-diagnosed multicentric DLBCL, MZL and FL that had undergone complete staging work-up and were treated with chemotherapy or chemo-immunotherapy. We developed a customized R pipeline performing a transcriptome assembly by multiple algorithms to uncover novel lncRNAs, and delineate genome-wide expression of unannotated and annotated lncRNAs. Our pipeline also included a new package for high performance system biology analysis, which detects high-scoring network biological neighborhoods to identify functional modules. Moreover, our customized pipeline quantified the expression of novel and annotated lncRNAs, allowing us to subtype DLBCLs into two main groups. The DLBCL subtypes showed statistically different survivals, indicating the potential use of lncRNAs as prognostic biomarkers in future studies.
In this manuscript, we describe the methodology used to identify lncRNAs that differentiate B-cell lymphoma subtypes and we interpreted the biological and clinical values of the results. We inferred the potential functions of lncRNAs to obtain a comprehensive and integrative insight that highlights their impact in this neoplasm.
弥漫性大B细胞淋巴瘤（DLBCL）、边缘区淋巴瘤（MZL）和滤泡性淋巴瘤（FL）是犬类中最常见的B细胞淋巴瘤（BCL）。最近的研究表明，这些组织学类型与人类的对应类型存在重叠，包括临床表现、生物学行为、肿瘤遗传学和治疗反应。犬类BCL的分子机制仍然未知，因此迫切需要开展新的研究以改善诊断、治疗，并将犬类作为自发性动物肿瘤模型加以利用。最近利用人类DLBCL转录组开展的研究表明，长链非编码RNA（lncRNA）在淋巴瘤发病机制中起关键作用，并确定了数量有限的lncRNA作为进一步研究的潜在靶点。
为了扩展对参与犬类BCL的非编码分子的认识，我们使用了从62只新诊断为多中心性DLBCL、MZL和FL的犬类队列中获得的转录组，这些犬类均已完成全面分期检查，并接受了化疗或化疗免疫治疗。我们开发了一个定制的R管道，通过多种算法进行转录组组装，以发现新的lncRNA，并描绘未注释和已注释lncRNA的全基因组表达。我们的管道还包括一个用于高性能系统生物学分析的新软件包，该软件包可检测高分网络生物学邻域以识别功能模块。此外，我们定制的管道对新的和已注释的lncRNA的表达进行了量化，使我们能够将DLBCL分为两个主要组。DLBCL亚型显示出统计学上不同的生存率，表明lncRNA在未来研究中作为预后生物标志物的潜在用途。
在本手稿中，我们描述了用于识别区分B细胞淋巴瘤亚型的lncRNA的方法，并解释了结果的生物学和临床价值。我们推断了lncRNA的潜在功能，以获得全面和综合的见解，突出它们在这种肿瘤中的影响。
