Abstract
BackgroundMicroRNAs (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.MethodsGlobal 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.ResultsmiRNA 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.ConclusionsOur 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.
Highlights
MicroRNAs are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis
In order to identify miRNA signatures that could serve as potential biomarkers to discriminate hereditary breast cancers (HBC), we evaluate the expression profiles of miRNAs in HBC tumors, sporadic breast cancer (SBC), and normal breast tissues (NBT) from carriers and non-carriers of BRCA1 or BRCA2 pathogenic germline mutations using NanoString technology
MiRNA expression profiling was performed on a total of 74 formalin-fixed paraffin-embedded (FFPE) samples, which comprised 43 HBC (15 BRCA1; 14 BRCA2; 14 BRCAX), 23 SBC and 8 NBT from 3 BRCA1-mutation carriers, 2 BRCA2-mutation carriers and 3 non-carriers
Summary
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. The most common entity linked to inherited breast cancer is the hereditary breast and ovarian cancer (HBOC) predisposition syndrome, which is a highly penetrant, autosomal dominant condition primarily caused by germline pathogenic variants in breast cancer type 1 and 2 susceptibility genes (BRCA1 and BRCA2) [3,4,5,6]. Female individuals who carry a BRCA1/2germline variant have a lifetime risk of developing breast cancer of up to 87% [11]. This may present a high histologic grade and, in particular for BRCA1-mutation carriers, a high mitotic index and triple-negative phenotype [12]. The identification of BRCA1/2-pathogenic variants is imperative and could directly impact on prevention, early cancer diagnosis, and clinical management of patients
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