miRNA expression profiling of inflammatory breast cancer identifies a 5‐miRNA signature predictive of breast tumor aggressiveness

Abstract

IBC (inflammatory breast cancer) is a rare but very aggressive form of breast cancer with a particular phenotype. The molecular mechanisms responsible for IBC remain largely unknown. In particular, genetic and epigenetic alterations specific to IBC remain to be identified. MicroRNAs, a class of small noncoding RNAs able to regulate gene expression, are deregulated in breast cancer and may therefore serve as tools for diagnosis and prediction. This study was designed to determine miRNA expression profiling (microRNAome) in IBC. Quantitative RT-PCR was used to determine expression levels of 804 miRNAs in a screening series of 12 IBC compared to 31 non-stage-matched non-IBC and 8 normal breast samples. The differentially expressed miRNAs were then validated in a series of 65 IBC and 95 non-IBC. From a set of 18 miRNAs of interest selected from the screening series, 13 were differentially expressed with statistical significance in the validation series of IBC compared to non-IBC. Among these, a 5-miRNA signature comprising miR-421, miR-486, miR-503, miR-720 and miR-1303 was shown to be predictive for IBC phenotype with an overall accuracy of 89%. Moreover, multivariate analysis showed that this signature was an independent predictor of poor Metastasis-Free Survival in non-IBC patients.IBC (inflammatory breast cancer) is a rare but very aggressive form of breast cancer with a unique phenotype.

Establishment of a prediction model for the miRNA-based heading date characteristics of rice in the booting stage

“…Similar results have been published for rice where the overexpression of miR156 increased leaf numbers, induced late flowering, and inhibited apical dominance (Gandikota et al, 2007). In recent studies, molecular models have enabled genomic selection for the prediction of genetic values in plants and animals (Crossa et al, 2010;de los Campos et al, 2012) and it was revealed that miRNA was a suitable molecular marker as it contains strong correlations between its expression profiling and the phenotypes observed (Lerebours et al, 2013). In this study, we have identified miRNA markers that predicted the heading date in rice, and may be used to improve breeding efficiency.…”

MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer

“…In addition, a 5-miRNA signature composed of miR-421, miR-486, MiR-503, miR-720, and miR-1303 was predictive for inflammatory breast cancer. 65 Apparently, the two published miRNA profiles in inflammatory breast cancer and our study results do not overlap. Small sample size may partly contribute to the lack of common profile.…”

“…Two miRNA profiling studies on inflammatory breast cancer by quantitative RT-PCR have been previously reported. 64,65 In one study, the authors evaluated the expression of 384 miRNAs in 20 inflammatory breast cancer and 50 noninflammatory breast cancer fresh frozen samples, and identified 13 miRNAs whose expression levels were different between inflammatory breast cancer and noninflammatory breast cancer, including 6 with increased expression in inflammatory breast cancer (miR-335, miR-337-5p, miR-451, miR-486-3p, miR-520a-5p, Table 6 Quantitative PCR results on eight miRNAs comparing inflammatory breast cancer and noninflammatory breast cancer samples qPCR normalized Ct value Normal (n = 11) Tumor (n = 45) IBC (n = 21) Non-IBC (n = 24) P-value tumor vs normal P-value IBC vs non-IBC and miR-548d-5p) and 7 with decreased expression in inflammatory breast cancer (miR-15a, miR-24, miR-29a, miR-30b, miR-320, miR-342-5p, and miR-342-3p). 64 In the other study, the expression of 804 miRNAs in 12 inflammatory breast cancer and 31 noninflammatory breast cancer human samples was examined, and the differentially expressed miRNAs were then validated in 65 inflammatory breast cancer and 95 noninflammatory breast cancer human samples.…”

Metastatic Heterogeneity of Breast Cancer Cells Is Associated with Expression of a Heterogeneous TGFβ-Activating miR424–503 Gene Cluster

“…Our current finding that Smad7 and Smurf2 protein levels are simultaneously and directly suppressed by overexpressed miR424-503 cluster in metastatic breast cancer cells without alterations in their mRNA levels, therefore, represents a novel posttranscriptional model for a coordinated regulation of these 2 factors. Although miRNAs have been reported to target Smad7 (36,37), and miR424 or miR503 overexpression has been separately found to be associated with poor prognosis in breast cancer (38,39), our results provides the first demonstration for miRNA Importantly, this newly identified mode of action is clinically relevant, as shown by our human specimens' data. Thus, a coordinated miRNA modulation of both Smad7 and Smurf2 appears to be an importantly new layer of TGFb signaling in breast cancer metastasis.…”