Translational Research Unit, Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium.
PLoS One. 2011;6(6):e20980. doi: 10.1371/journal.pone.0020980. Epub 2011 Jun 29.
Aberrant microRNA (miRNA) expression is associated with cancer and has potential diagnostic and prognostic value in various malignancies. In this study, we investigated miRNA profiling as a complementary tool to improve our understanding of breast cancer (BC) biology and to assess whether miRNA expression could predict clinical outcome of BC patients.
Global miRNA expression profiling using microarray technology was conducted in 56 systemically untreated BC patients who had corresponding mRNA expression profiles available. Results were further confirmed using qRT-PCR in an independent dataset of 89 ER-positive BC patients homogeneously treated with tamoxifen only. MiR-210 functional analyses were performed in MCF7 and MDA-MB-231 BC cell lines using lentiviral transduction.
Estrogen receptor (ER) status, tumor grade and our previously developed gene expression grade index (GGI) were associated with distinct miRNA profiles. Several miRNAs were found to be clinically relevant, including miR-210, its expression being associated with tumor proliferation and differentiation. Furthermore, miR-210 was associated with poor clinical outcome in ER-positive, tamoxifen-treated BC patients. Interestingly, the prognostic performance of miR-210 was similar to several reported multi-gene signatures, highlighting its important role in BC differentiation and tumor progression. Functional analyses in BC cell lines revealed that miR-210 is involved in cell proliferation, migration and invasion.
This integrated analysis combining miRNA and mRNA expression demonstrates that miRNA expression provides additional biological information beyond mRNA expression. Expression of miR-210 is linked to tumor proliferation and appears to be a strong potential biomarker of clinical outcome in BC.
异常的 microRNA（miRNA）表达与癌症相关，在各种恶性肿瘤中具有潜在的诊断和预后价值。在这项研究中，我们研究了 miRNA 谱分析，作为一种补充工具，以增进我们对乳腺癌（BC）生物学的理解，并评估 miRNA 表达是否可以预测 BC 患者的临床结局。
使用微阵列技术对 56 例未经系统治疗的 BC 患者进行了全局 miRNA 表达谱分析，这些患者有相应的 mRNA 表达谱可供使用。在使用仅接受他莫昔芬治疗的 89 例 ER 阳性 BC 患者的独立数据集上，进一步使用 qRT-PCR 进行了结果验证。在 MCF7 和 MDA-MB-231 BC 细胞系中，使用慢病毒转导进行了 miR-210 功能分析。
雌激素受体（ER）状态、肿瘤分级和我们之前开发的基因表达分级指数（GGI）与不同的 miRNA 谱相关。发现几种 miRNA 具有临床相关性，包括 miR-210，其表达与肿瘤增殖和分化有关。此外，miR-210 与 ER 阳性、接受他莫昔芬治疗的 BC 患者的不良临床结局相关。有趣的是，miR-210 的预后性能与几个报道的多基因签名相似，突出了其在 BC 分化和肿瘤进展中的重要作用。BC 细胞系中的功能分析表明，miR-210 参与细胞增殖、迁移和侵袭。
这项结合 miRNA 和 mRNA 表达的综合分析表明，miRNA 表达提供了超出 mRNA 表达的额外生物学信息。miR-210 的表达与肿瘤增殖有关，似乎是 BC 临床结局的一个强有力的潜在生物标志物。
