Division of Surgery and Cancer, Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
PLoS One. 2011 Feb 22;6(2):e16915. doi: 10.1371/journal.pone.0016915.
Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information.
We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods.
We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process.
This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.
很少有研究从同一原发性乳腺癌中同时对 miRNA 和 mRNA 进行表达谱分析。在这项研究中，我们呈现并分析了从 101 例原发性人乳腺癌中 799 个 miRNA 的表达谱、全基因组 mRNA 谱以及广泛的临床信息。
我们根据彼此之间以及与临床特征的相关性来研究这些分子成分之间的关系。我们使用系统生物学方法，使用统计富集方法来检查 miRNA 和 mRNAs 之间的相关关系。
我们发现 miRNA 在分子固有亚型之间以及增殖水平不同的样本之间存在统计学显著的差异表达。具体而言，我们指出了与 TP53 和 ER 状态显著相关的 miRNA。我们还表明，某些细胞过程，如增殖、细胞黏附和免疫反应，与某些 miRNA 密切相关。我们使用细胞系上的高通量裂解物微阵列验证了 miRNA 在调节增殖中的作用，并指出了这一过程的潜在驱动因素。
这项研究提供了一个全面的数据集以及方法和系统水平的结果，为进一步研究 miRNA 在原发性乳腺癌中的作用奠定了基础。
