Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
Department of Breast and Reconstructive Surgery, Barretos Cancer Hospital, Barretos, SP, Brazil.
BMC Cancer. 2020 Feb 22;20(1):143. doi: 10.1186/s12885-020-6640-y.
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. Aberrant miRNA expression has been frequently reported in sporadic breast cancers, but few studies have focused on profiling hereditary breast cancers. In this study, we aimed to identify specific miRNA signatures in hereditary breast tumors and to compare with sporadic breast cancer and normal breast tissues.
Global miRNA expression profiling using NanoString technology was performed on 43 hereditary breast tumors (15 BRCA1, 14 BRCA2, and 14 BRCAX), 23 sporadic breast tumors and 8 normal breast tissues. These normal breast tissues derived from BRCA1- and BRCA2- mutation carriers (n = 5) and non-mutation carriers (n = 3). Subsequently, we performed receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performance of differentially expressed miRNAs. Putative target genes of each miRNAs considered as potential biomarkers were identified using miRDIP platform and used for pathway enrichment analysis.
miRNA expression analyses identified several profiles that were specific to hereditary breast cancers. A total of 25 miRNAs were found to be differentially expressed (fold change: > 2.0 and p < 0.05) and considered as potential biomarkers (area under the curve > 0.75) in hereditary breast tumors compared to normal breast tissues, with an expressive upregulation among BRCAX cases. Furthermore, bioinformatic analysis revealed that these miRNAs shared target genes involved in ErbB, FoxO, and PI3K-Akt signaling pathways.
Our results showed that miRNA expression profiling can differentiate hereditary from sporadic breast tumors and normal breast tissues. These miRNAs were remarkably deregulated in BRCAX hereditary breast cancers. Therefore, miRNA signatures can be used as potential novel diagnostic biomarkers for the prediction of BRCA1/2- germline mutations and may be useful for future clinical management.
微小 RNA（miRNA）是参与转录后基因表达调控的小非编码 RNA，被描述为癌发生的关键调节因子。散发性乳腺癌中经常报道 miRNA 表达异常，但很少有研究集中于遗传性乳腺癌的分析。在这项研究中，我们旨在鉴定遗传性乳腺癌肿瘤中的特定 miRNA 特征，并与散发性乳腺癌和正常乳腺组织进行比较。
使用 NanoString 技术对 43 例遗传性乳腺癌（15 例 BRCA1、14 例 BRCA2 和 14 例 BRCAX）、23 例散发性乳腺癌和 8 例正常乳腺组织进行了全 miRNA 表达谱分析。这些正常乳腺组织来源于 BRCA1 和 BRCA2 突变携带者（n=5）和非突变携带者（n=3）。随后，我们进行了接收器操作特征（ROC）曲线分析，以评估差异表达 miRNA 的诊断性能。使用 miRDIP 平台鉴定每个 miRNA 的假定靶基因，并用于途径富集分析。
miRNA 表达分析确定了一些特异性的遗传性乳腺癌特征。与正常乳腺组织相比，遗传性乳腺癌中发现 25 个 miRNA 表达差异（倍数变化：>2.0 和 p<0.05），并被认为是潜在的生物标志物（曲线下面积>0.75），BRCAX 病例中表达上调。此外，生物信息学分析显示，这些 miRNA 共享参与 ErbB、FoxO 和 PI3K-Akt 信号通路的靶基因。
我们的结果表明，miRNA 表达谱分析可区分遗传性和散发性乳腺癌以及正常乳腺组织。这些 miRNA 在 BRCAX 遗传性乳腺癌中显著失调。因此，miRNA 特征可作为预测 BRCA1/2 种系突变的潜在新型诊断生物标志物，可能对未来的临床管理有用。
