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MiRNA expression profiling in hereditary breast tumors

ABSTRACT: The objective of the study was to characterize hereditary breast tumors based on their miRNA expression profiles. To this end, we performed global miRNA expression analysis of more than 800 human miRNA genes in a large series of 80 FFPE breast tissue samples. The series included 66 hereditary breast primary tumors from 13 BRCA1 mutation carriers, 10 BRCA2 mutation carriers and 43 non-BRCA12 tumors denominated hereafter as BRCAX tumors. In addition we have analyzed 10 sporadic breast carcinomas and 4 normal breast tissues obtained after breast reduction surgery from healthy donors with no family history of breast cancer. To avoid contamination with normal breast tissue, tumoral area on FFPE blocks was marked by a pathologist and macrodissected for subsequent total RNA extraction. Microarray expression profiling was performed using miRCURY LNATM microRNA Array v.11 (Exiqon A/S, Denmark), in a single color experiments in a pairwise comparison experimantal design.

ORGANISM(S): Homo sapiens

SUBMITTER: Tanic Miljana

PROVIDER: S-ECPF-GEOD-44899 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

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MiRNA expression profiling in hereditary breast tumors

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