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深度测序揭示了乳腺浸润性微乳头状癌的小 RNA 特征。

Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast.

机构信息

Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.

出版信息

Breast Cancer Res Treat. 2012 Nov;136(1):77-87. doi: 10.1007/s10549-012-2166-6. Epub 2012 Sep 14.

DOI:10.1007/s10549-012-2166-6
PMID:22976804
Abstract

Invasive micropapillary carcinoma (IMPC) is an uncommon histological type of breast cancer. IMPC has a special growth pattern and a more aggressive behavior than invasive ductal carcinomas of no special types (IDC-NSTs). microRNAs are a large class of non-coding RNAs involved in the regulation of various biological processes. Here, we analyzed the small RNA transcriptomes of five formalin-fixed paraffin-embedded (FFPE) pure IMPC samples and five FFPE IDC-NSTs samples by means of next-generation sequencing, generating a total of >170,000,000 clean reads. In an unsupervised cluster analysis, differently expressed miRNAs generated a tree with clear distinction between IMPC and IDC-NSTs classes. Paired fresh-frozen and FFPE specimens showed very similar miRNA expression profiles. By means of RT-qPCR, we further investigated miRNA expression in more IMPC (n = 22) and IDC-NSTs (n = 24) FFPE samples and found let-7b, miR-30c, miR-148a, miR-181a, miR-181a*, and miR-181b were significantly differently expressed between the two groups. We also elucidated several features of miRNA in these breast cancer tissues including 5' variability, miRNA editing, and 3' untemplated addition. Our findings will lead to further understanding of the invasive potency of IMPC and gain an insight into the diversity and complexity of small RNA molecules in breast cancer tissues.

摘要

浸润性微乳头状癌(IMPC)是一种罕见的乳腺癌组织学类型。与非特殊型浸润性导管癌(IDC-NST)相比,IMPC 具有特殊的生长模式和更具侵袭性的行为。microRNAs 是一大类非编码 RNA,参与调节各种生物过程。在这里,我们通过下一代测序分析了 5 个福尔马林固定石蜡包埋(FFPE)纯 IMPC 样本和 5 个 FFPE IDC-NST 样本的小 RNA 转录组,总共产生了超过 170,000,000 个清洁读数。在无监督聚类分析中,差异表达的 microRNAs 生成了一棵清晰区分 IMPC 和 IDC-NSTs 类别的树。配对的新鲜冷冻和 FFPE 标本显示出非常相似的 microRNA 表达谱。通过 RT-qPCR,我们进一步研究了更多的 IMPC(n=22)和 IDC-NSTs(n=24)FFPE 样本中的 microRNA 表达,发现 let-7b、miR-30c、miR-148a、miR-181a、miR-181a*和 miR-181b 在两组之间的表达存在显著差异。我们还阐明了这些乳腺癌组织中 microRNA 的几个特征,包括 5'变异性、microRNA 编辑和 3'无模板添加。我们的发现将进一步加深对 IMPC 侵袭能力的理解,并深入了解乳腺癌组织中小 RNA 分子的多样性和复杂性。

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