Circulating Cell-free miRNA Expression and its Association with Clinicopathologic Features in Inflammatory and Non-Inflammatory Breast Cancer

Abstract

Recent discovery showing the presence of microRNAs (miRNAs) in the circulation sparked interest in their use as potential biomarkers. Our previous studies showed the diagnostic potential of miR-451 as a serological marker for inflammatory breast cancer (IBC), miR-337-5p and miR-30b for non-inflammatory breast cancer (non-IBC). The aim of this study is to investigate the prognostic values of circulating miRNAs by comparing the amounts of 12 circulating miRNAs in the serum of IBC and non-IBC from Tunisian breast cancer patients, and by determinating whether correlated pairs of miRNAs could provide useful information in the diagnosis of IBC and non-IBC patients. TaqMan qPCR was performed to detect circulating expression of miRNAs in serum of 20 IBC, 20 non-IBC and 20 healthy controls. Nonparametric rank Spearman rho correlation coefficient was used to examine the prognostic value of miRNAs and to assess the correlation profile between miRNAs expression. Further, a large number of miRNAs were highly correlated (rho>0.5) in both patients groups and controls. Also, the correlations profiles were different between IBC, non-IBC and healthy controls indicating important changes in molecular pathways in cancer cells. Our results showed that miR-335 was significantly overexpressed in premenopausal non-IBC patients; miR-24 was significantly overexpressed in non-IBC postmenopausal patients. Patients with previous parity had higher serum of miR-342-5p levels than those without. Furthermore, patients with HER2+ IBC present lower serum levels of miR-15a than patients with HER2-disease. Together, these results underline the potential of miRNAs to function as diagnostic and prognostic markers for IBC and non-IBC, with links to the menopausal state, Her2 status and parity.

Expression signatures and roles of microRNAs in inflammatory breast cancer

“…miR-451 is found obviously down-regulated in IBC patients when compared to normal sera, providing credible evidence for miR-451 being considered as a new serological bio-marker for IBC, which is derived from a study led by Khouloud et al and Hamdi et al [21, 37]. In this regard, one possible explanation accounting for this phenomenon is that exosomes containing miR-451 are cut off 57.5-fold.…”

“…Furthermore, by means of targeting Cyclin E1 directly, miR-15a also play a major role in promoting cell apoptosis and mediating cell-cycle arrest of breast cancer, make it clear that miR-15a possesses tumor suppressive activity in a cell line of breast cancer [45, 46]. In addition, due to the discovery of HER2/neu-induced miR-15a restrain, a better understanding about how HER2/neu over-expression accelerates metastasis and invasion of IBC cells is well provided [37]. All these connections between miR-15a and HER2 status indicate that HER-2 signalization is worthy to have a place in the regulation of miR-15a in IBC and miR-15a can be a considerable molecular bio-marker for assessing HER2 status in IBC [37].…”

“…In addition, due to the discovery of HER2/neu-induced miR-15a restrain, a better understanding about how HER2/neu over-expression accelerates metastasis and invasion of IBC cells is well provided [37]. All these connections between miR-15a and HER2 status indicate that HER-2 signalization is worthy to have a place in the regulation of miR-15a in IBC and miR-15a can be a considerable molecular bio-marker for assessing HER2 status in IBC [37].

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“…(4) Serum/plasma samples are available conveniently and non-invasively, and the levels of miRNAs can also be easily measured by multifarious common and mature detection technology [34, 35]. All these findings show that, as a novel, safe and non-invasive bio-marker, miRNAs will furnish considerable diagnostic and prognostic values on IBC and non-IBC diseases by restoring or antagonizing their expression [36, 37].…”

Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

“…Hamdi et al [54] analyzed circulating miRNA expression in inflammatory and non-inflammatory BC and described lower miR-15a serum levels in the HER2+ subtype, offering a distinctive element for such a BC subgroup.…”