Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer
Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer
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DOI：
10.1073/pnas.0803304105
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发表时间：
2008-09-02
影响因子：
11.1
通讯作者：
Martens, John W. M.
中科院分区：
文献类型：
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作者：
Foekens, John A.;Sieuwerts, Anieta M.;Martens, John W. M.
在这项研究中，我们量化了淋巴结阴性（LNN）患者的雌激素受体阳性（ER+）原发性乳腺肿瘤中249种成熟的微rna （miRNA）转录物，以鉴定与转移能力相关的miRNA。此外，还确定了候选mirna在ER-/LNN乳腺癌中的预后价值。在一组38名患者的预筛选中，无监督分析确定了三个主要由三种miRNA信号驱动的亚组：er驱动的腔内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，但这些内在miRNA信号与肿瘤侵袭性无关。在初始亚组的监督分析和其他肿瘤的后续分析中，4种miRNA （miR-7、miR-128a、miR-210和miR-516-3p）与ER+/LNN乳腺癌的侵袭性（n = 147）和1种miRNA （miR-210）与ER-/LNN乳腺癌（n = 114）和临床重要三阴性亚组（n = 69）的转移能力显著相关（均P < 0.05）。生物信息学分析将miR-210与缺氧/VEGF信号联系起来，miR-7和miR-516-3p与细胞周期进程和染色体不稳定性联系起来，miR-128a与细胞因子信号联系起来。总之，我们的工作将四种mirna与乳腺癌的进展以及其中涉及的几种不同的生物学过程联系起来。
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). Bioinformatic 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.