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.

Highlights

  • MicroRNAs are small noncoding RNA oligonucleotides (22-25 nucleotides) that suppress gene expression post-transcriptionally via sequence-specific interactions with cognate mRNA targets, they suppress translation and induce degradation of mRNAs

  • 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 inflammatory breast cancer (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

  • This study is a continuity of our previous study in which we have shown that miR-451could be considered as a serological marker for IBC

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Summary

Introduction

MicroRNAs (miRNAs) are small noncoding RNA oligonucleotides (22-25 nucleotides) that suppress gene expression post-transcriptionally via sequence-specific interactions with cognate mRNA targets, they suppress translation and induce degradation of mRNAs. Dysregulation of the expression of miRNAs results in diverse disease states (Sayed and Abdellatif, 2011). Aberrations in miRNAs expression levels influence the occurrence and development of tumor and have been linked to the onset and progression of various types of cancer (Palmero et al, 2011). In this particular context, the roles of miRNAs in carcinogenesis and tumor progression are mainly associated with miRNA-regulated expression of oncogenes and tumor suppressor genes (Croce, 2009). The overexpression of certain miRNAs could lead to the repression of tumor suppressor genes. MiRNAs down-regulation could result in increased oncogene expression (Li et al, 2013). In previous work it has been demonstrated that extracellular miRNAs levels are surprisingly stable in body fluids ,retrievable and measurable from fresh or archival serum and plasma samples (Chen et al, 2008; Mitchell et al, 2008; Schwarzenbach et al, 2014)

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