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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer
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Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer

机译：四种miRNA与淋巴结阴性，雌激素受体阳性的人乳腺癌的侵袭性相关

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摘要

In this study, we quantified 249 mature micro-RNA (miRNA) transcripts in estrogen receptor-positive (ER~+) primary breast tumors of patients with lymph node-negative (LNN) disease to identify miRNAs associated with metastatic capability. In addition, the prognostic value of the candidate miRNAs was determined in ER~-/LNN breast cancer. Unsupervised analysis in a prescreening set of 38 patients identified three subgroups predominantly driven by three miRNA signatures: an ER-driven luminal B-associated miRNA signature, a stromal miRNA signature, and an overexpressed miRNA cluster located on chromosome 19q23, but these intrinsic miRNA signatures were not associated with tumor aggressiveness. Supervised analysis in the initial subset and subsequent analysis in additional tumors significantly linked four miRNAs (miR-7, miR-128a. miR-210. and miR-516-3p) to ER~+/LNN breast cancer aggressiveness (n = 147) and one miRNA (miR-210) to metastatic capability in ER~/LNN breast cancer (n = 114) and in the clinically important triple-negative subgroup (n = 69) (all P < 0.05). Bioin-formatic analysis coupled miR-210 to hypoxia/VEGF signaling, miR-7 and miR-516-3p to cell cycle progression and chromosomal instability, and miR-128a to cytokine signaling. In conclusion, our work connects four miRNAs to breast cancer progression and to several distinct biological processes involved therein.
机译：在这项研究中，我们量化了淋巴结阴性（LNN）疾病患者的雌激素受体阳性（ER〜+）原发性乳腺肿瘤中的249个成熟microRNA（miRNA）转录本，以鉴定与转移能力相关的miRNA。另外，在ER〜// LNN乳腺癌中确定了候选miRNA的预后价值。在38名患者的预筛查中进行无监督分析，确定了三个亚组，主要由三个miRNA信号驱动：ER驱动的管腔B相关miRNA信号，基质miRNA信号和位于染色体19q23上的过表达miRNA簇，但是这些固有的miRNA信号与肿瘤侵袭性无关。在初始子集中进行的监督分析以及对其他肿瘤的后续分析将四种miRNA（miR-7，miR-128a，miR-210。和miR-516-3p）与ER〜+ / LNN乳腺癌侵袭性相关联（n = 147）在ER〜/ LNN乳腺癌（n = 114）和临床上重要的三阴性亚组（n = 69）中有一种miRNA（miR-210）具有转移能力（所有P <0.05）。生物信息学分析将miR-210耦合到缺氧/ VEGF信号传导，将miR-7和miR-516-3p耦合到细胞周期进程和染色体不稳定，并将miR-128a耦合到细胞因子信号传导。总之，我们的工作将四个miRNA与乳腺癌的进展以及其中涉及的几个不同的生物学过程联系起来。

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