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首页> 外文期刊>BMC Medical Genomics >Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers
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Progression-specific genes identified in microdissected formalin-fixed and paraffin-embedded tissue containing matched ductal carcinoma in situ and invasive ductal breast cancers

机译：在显微解剖的福尔马林固定和石蜡包埋组织中鉴定的特定于进展的基因，其中包含匹配的原位导管癌和浸润性导管癌

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The transition from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) is an important step during breast carcinogenesis. Understanding its molecular changes may help to identify high-risk DCIS that progress to IBC. Here, we describe a transcriptomic profiling analysis of matched formalin-fixed and paraffin-embedded (FFPE) DCIS and IBC components of individual breast tumours, containing both tumour compartments. The study was performed to validate progression-associated transcripts detected in an earlier gene profiling project using fresh frozen breast cancer tissue. In addition, FFPE tissues from patients with pure DCIS (pDCIS) were analysed to identify candidate transcripts characterizing DCIS with a high or low risk of progressing to IBC. Fifteen laser microdissected pairs of DCIS and IBC were profiled by Illumina DASL technology and used for expression validation by qPCR. Differential expression was independently validated using further 25 laser microdissected DCIS/IBC sample pairs. Additionally, laser microdissected epithelial cells from 31 pDCIS were investigated for expression of candidate transcripts using qPCR. Multiple statistical calculation methods revealed 1784 mRNAs which are differentially expressed between DCIS and IBC (P??0.05), of which 124 have also been identified in the gene profiling project using fresh frozen breast cancer tissue. Nine mRNAs that had been selected from the gene list obtained using fresh frozen tissues by applying pathway and network analysis (MMP11, GREM1, PLEKHC1, SULF1, THBS2, CSPG2, COL10A1, COL11A1, KRT14) were investigated in tissues from the same 15 microdissected specimens and the 25 independent tissue samples by qPCR. All selected transcripts were also detected in tumour cells from pDCIS. Expression of MMP11 and COL10A1 increased significantly from pDCIS to DCIS of DCIS/IBC mixed tumours. We confirm differential expression of progression-associated transcripts in FFPE breast cancer samples which might mediate the transition from DCIS to IBC. MMP11 and COL10A1 may characterize pure DCIS with a high risk developing IDC.
机译：从乳腺导管原位癌（DCIS）转变为浸润性乳腺癌（IBC）是乳腺癌致癌过程中的重要一步。了解其分子变化可能有助于鉴定发展为IBC的高风险DCIS。在这里，我们描述了包含两个肿瘤区室的单个乳腺肿瘤的匹配福尔马林固定和石蜡包埋（FFPE）DCIS和IBC成分的转录组分析。进行该研究以验证使用新鲜的冷冻乳腺癌组织在较早的基因分析项目中检测到的与进展相关的转录本。此外，对来自纯DCIS（pDCIS）患者的FFPE组织进行了分析，以鉴定出具有发展为IBC的高风险或低风险的DCIS的候选转录本。通过Illumina DASL技术分析了15对激光显微切割的DCIS和IBC对，并通过qPCR用于表达验证。使用另外的25个激光显微切割的DCIS / IBC样品对独立验证了差异表达。此外，使用qPCR研究了来自31 pDCIS的激光显微切割的上皮细胞的候选转录本表达。多种统计计算方法揭示了1784个在DCIS和IBC之间差异表达的mRNA（P 0.05），其中在使用新鲜冷冻乳腺癌组织的基因谱分析项目中也鉴定出了124个。在15个经过显微解剖的组织样本中，对通过使用途径和网络分析从使用新鲜冷冻组织获得的基因列表中选择的9种mRNA（MMP11，GREM1，PLEKHC1，SULF1，THBS2，CSPG2，COL10A1，COL11A1，KRT14）进行了研究通过qPCR检测25个独立的组织样本。在pDCIS的肿瘤细胞中也检测到所有选定的转录物。从pDCIS到DCIS / IBC混合肿瘤的DCIS，MMP11和COL10A1的表达显着增加。我们证实FFPE乳腺癌样品中与进展相关的转录本的差异表达可能介导从DCIS到IBC的过渡。 MMP11和COL10A1可能表征具有发展IDC的高风险的纯DCIS。

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