Integrated microRNA and mRNA signatures associated with survival in triple negative breast cancer.
Integrated microRNA and mRNA signatures associated with survival in triple negative breast cancer.
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DOI：
10.1371/journal.pone.0055910
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Huebner K
中科院分区：
文献类型：
--
作者：
Cascione L;Gasparini P;Lovat F;Carasi S;Pulvirenti A;Ferro A;Alder H;He G;Vecchione A;Croce CM;Shapiro CL;Huebner K
三阴性乳腺癌（TNBC）在分子、病理和临床水平上是一种异质性疾病。为了对 TNBC 进行分层，我们确定了 173 名 TNBC 女性的肿瘤、邻近非肿瘤（正常）和淋巴结转移性病变 (mets) 组织中的 microRNA (miRNA) 表达谱以及癌症聚焦 mRNA 组的表达谱；我们将特定的 miRNA 特征与患者生存联系起来，并使用 miRNA/mRNA 反相关性来识别临床和遗传上不同的 TNBC 亚类。我们还评估了 miRNA 特征作为由典型信号通路的表达定义的 TNBC 亚类特异性基因表达网络的潜在调节因子。鉴定组织特异性 miRNA 和 mRNA，用于正常、肿瘤、mets 比较。鉴定了与预后相关的 miRNA 特征，并定义了 mRNA 谱中预测的反相关目标。确定了患者的两个 miRNA 特征（miR-16、155、125b、374a 和 miR-16、125b、374a、374b、421、655、497）分别预测患者的总生存期（P = 0.05）和远处无病生存期（P = 0.009） 50岁或以下。通过多变量分析，风险特征是总生存期和远处无病生存期的独立预测因子。使用以癌症为中心的 mRNA 组进行 mRNA 表达谱分析，将 TNBC 聚类为 4 个分子亚类，这些亚类具有与预后 miRNA 反相关的不同表达特征。我们的研究结果表明，miRNA 通过其调节基本途径的能力在三阴性乳腺癌中发挥关键作用，例如：细胞生长和增殖、细胞运动和迁移、细胞外基质降解。结果定义了 miRNA 表达特征，这些特征表征并促进了 TNBC 及其转移的表型多样性。
Triple negative breast cancer (TNBC) is a heterogeneous disease at the molecular, pathologic and clinical levels. To stratify TNBCs, we determined microRNA (miRNA) expression profiles, as well as expression profiles of a cancer-focused mRNA panel, in tumor, adjacent non-tumor (normal) and lymph node metastatic lesion (mets) tissues, from 173 women with TNBCs; we linked specific miRNA signatures to patient survival and used miRNA/mRNA anti-correlations to identify clinically and genetically different TNBC subclasses. We also assessed miRNA signatures as potential regulators of TNBC subclass-specific gene expression networks defined by expression of canonical signal pathways. Tissue specific miRNAs and mRNAs were identified for normal vs tumor vs mets comparisons. miRNA signatures correlated with prognosis were identified and predicted anti-correlated targets within the mRNA profile were defined. Two miRNA signatures (miR-16, 155, 125b, 374a and miR-16, 125b, 374a, 374b, 421, 655, 497) predictive of overall survival (P = 0.05) and distant-disease free survival (P = 0.009), respectively, were identified for patients 50 yrs of age or younger. By multivariate analysis the risk signatures were independent predictors for overall survival and distant-disease free survival. mRNA expression profiling, using the cancer-focused mRNA panel, resulted in clustering of TNBCs into 4 molecular subclasses with different expression signatures anti-correlated with the prognostic miRNAs. Our findings suggest that miRNAs play a key role in triple negative breast cancer through their ability to regulate fundamental pathways such as: cellular growth and proliferation, cellular movement and migration, Extra Cellular Matrix degradation. The results define miRNA expression signatures that characterize and contribute to the phenotypic diversity of TNBC and its metastasis.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
在癌症转移中重新审视种子和土壤。
DOI：
10.1016/j.biocel.2009.01.015
发表时间：
2009-07
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Mendoza M;Khanna C
通讯作者：
Khanna C
影响因子：
2.5
作者：
Howe EN;Cochrane DR;Richer JK
通讯作者：
Richer JK
影响因子：
3.4
作者：
Di Leva G;Briskin D;Croce CM
通讯作者：
Croce CM
DOI：
10.1158/1541-7786.mcr-11-0500
发表时间：
2012-01
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Garimella SV;Rocca A;Lipkowitz S
通讯作者：
Lipkowitz S