Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers.
Expression profiling of cancerous and normal breast tissues identifies microRNAs that are differentially expressed in serum from patients with (metastatic) breast cancer and healthy volunteers.
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DOI：
10.1186/bcr3127
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发表时间：
2012-02-21
期刊：
影响因子：
--
通讯作者：
Van Laere SJ
中科院分区：
文献类型：
--
作者：
van Schooneveld E;Wouters MC;Van der Auwera I;Peeters DJ;Wildiers H;Van Dam PA;Vergote I;Vermeulen PB;Dirix LY;Van Laere SJ
MicroRNA (miRNA) 是一组参与基因表达调控的小非编码 RNA。因此，它们调节大量细胞通路，并且 miRNA 表达失调或改变与肿瘤发生相关。在当前的研究中，我们评估了循环 miRNA 作为乳腺癌检测和分期生物标志物的可行性和临床实用性。从乳腺癌患者的 84 个组织样本和乳房缩小手术后获得的 8 个正常组织样本中提取了 miRNA。逆转录和预扩增后，使用 TaqMan 低密度阵列对 768 个 miRNA 进行了分析。数据标准化后，使用无监督层次聚类分析 (UHCA) 来研究癌症和正常样本之间 miRNA 表达的整体差异。通过倍数变化分析，选择了两种组织类型之间最具区别性的 miRNA，并在 20 名健康志愿者和 75 名乳腺癌患者（包括 16 名未经治疗的转移性乳腺癌患者）的血清样本中分析了它们的表达。从 200 μl 血清中提取 miRNA，进行反转录，并使用聚合酶链反应 (qRT-PCR) 进行重复分析。 UHCA 显示乳腺癌患者组织样本和乳房缩小手术组织样本之间 miRNA 表达存在显着差异 (P < 0.0001)。一般来说，与健康对照中的 miRNA 表达相比，癌症样本中的 miRNA 表达往往受到抑制 (P = 0.0685)。选择倍数变化最有区别的四种 miRNA（miR-215、miR-299-5p、miR-411 和 miR-452）用于对血清样本进行进一步分析。所有 miRNA 至少在癌症患者血清样本和健康对照血清样本之间存在差异表达（miR-215，P = 0.094；miR-299-5P，P = 0.019；miR-411，P = 0.002；miR-452，P = 0.092）。对于所有这些 miRNA，除了 miR-452 外，在健康志愿者的血清样本和未经治疗的转移性乳腺癌患者的血清样本之间观察到最大的表达差异。我们的研究为建立 miRNA 作为通过血源性检测检测乳腺癌并最终进行分期的生物标志物奠定了基础。我们鉴定并测试了一组假定的乳腺癌生物标志物，并证明乳腺癌患者血清中这些 miRNA 水平的改变与转移性疾病的存在特别相关。
MicroRNAs (miRNAs) are a group of small noncoding RNAs involved in the regulation of gene expression. As such, they regulate a large number of cellular pathways, and deregulation or altered expression of miRNAs is associated with tumorigenesis. In the current study, we evaluated the feasibility and clinical utility of circulating miRNAs as biomarkers for the detection and staging of breast cancer. miRNAs were extracted from a set of 84 tissue samples from patients with breast cancer and eight normal tissue samples obtained after breast-reductive surgery. After reverse transcription and preamplification, 768 miRNAs were profiled by using the TaqMan low-density arrays. After data normalization, unsupervised hierarchical cluster analysis (UHCA) was used to investigate global differences in miRNA expression between cancerous and normal samples. With fold-change analysis, the most discriminating miRNAs between both tissue types were selected, and their expression was analyzed on serum samples from 20 healthy volunteers and 75 patients with breast cancer, including 16 patients with untreated metastatic breast cancer. miRNAs were extracted from 200 μl of serum, reverse transcribed, and analyzed in duplicate by using polymerase chain reaction (qRT-PCR). UHCA showed major differences in miRNA expression between tissue samples from patients with breast cancer and tissue samples from breast-reductive surgery (P < 0.0001). Generally, miRNA expression in cancerous samples tends to be repressed when compared with miRNA expression in healthy controls (P = 0.0685). The four most discriminating miRNAs by fold-change (miR-215, miR-299-5p, miR-411, and miR-452) were selected for further analysis on serum samples. All miRNAs at least tended to be differentially expressed between serum samples from patients with cancer and serum samples from healthy controls (miR-215, P = 0.094; miR-299-5P, P = 0.019; miR-411, P = 0.002; and miR-452, P = 0.092). For all these miRNAs, except for miR-452, the greatest difference in expression was observed between serum samples from healthy volunteers and serum samples from untreated patients with metastatic breast cancer. Our study provides a basis for the establishment of miRNAs as biomarkers for the detection and eventually staging of breast cancer through blood-borne testing. We identified and tested a set of putative biomarkers of breast cancer and demonstrated that altered levels of these miRNAs in serum from patients with breast cancer are particularly associated with the presence of metastatic disease.
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影响因子：
7.3
作者：
Bombonati, Alessandro;Sgroi, Dennis C.
通讯作者：
Sgroi, Dennis C.
DOI：
10.1073/pnas.0912708107
发表时间：
2010-04-13
影响因子：
11.1
作者：
Gatza, Michael L.;Lucas, Joseph E.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.
影响因子：
5.3
作者：
Duan, Zhijun;Person, Richard E.;Horwitz, Marshall S.
通讯作者：
Horwitz, Marshall S.
DOI：
10.1073/pnas.0906947106
发表时间：
2009-09-15
影响因子：
11.1
作者：
Castellano, Leandro;Giamas, Georgios;Stebbing, Justin
通讯作者：
Stebbing, Justin
影响因子：
3.7
作者：
Hunter, Melissa Piper;Ismail, Noura;Zhang, Xiaoli;Aguda, Baltazar D.;Lee, Eun Joo;Yu, Lianbo;Xiao, Tao;Schafer, Jeffrey;Lee, Mei-Ling Ting;Schmittgen, Thomas D.;Nana-Sinkam, S. Patrick;Jarjoura, David;Marsh, Clay B.
通讯作者：
Marsh, Clay B.