Abstract

In recent years, circulating miRNAs have attracted interest as stable, non-invasive biomarkers for various pathological conditions. Here, we investigated their potential to serve as minimally invasive, early detection markers for inflammatory breast cancer (IBC) and non-inflammatory breast cancer (non-IBC) in serum. miRNA profiling was performed on serum from 20 patients with non-IBC, 20 with IBC, and 20 normal control subjects. Real-time reverse transcription-polymerase chain reaction (qRT-PCR) was applied to measure the level of 12 candidate miRNAs previously identified in other research(miR-342-5p, miR-342--3p, miR-320, miR-30b, miR-29a, miR-24, miR-15a, miR-548d-5p, miR-486-3p, miR-451, miR-337-5p, miR-335).We found that 4 miRNAs (miR-24, miR-342-3p, miR-337-5p and miR-451) were differentially expressed in serum of IBC patients compared to non-IBC, and 3 miRNAs (miR-337-5p ,miR-451and miR-30b) were differentially expressed in IBC and non-IBC patients combined compared to healthy controls. miR-24, miR-342-3p, miR-337-5p and miR-451 were found to be significantly down-regulated in IBC patients compared to non-IBC. Likewise, the expression level of mir-451 showed significant down-regulation in IBC serum, while mir-30b and miR-337-5p were up-regulated in non-IBC serum comparatively to normal controls. Using receiver operational curve (ROC) analysis, we show that dysregulated miRNAs can discriminate patients with IBC and non-IBC from healthy controls with sensitivity ranging from 76 to 81% and specificity from 66 to 80%, for three separate miRNAs. In conclusion, our data suggest that circulating miRNAs are potential biomarkers for classifying IBC and non-IBC, and may also be candidates for early detection of breast cancer.

Highlights

  • Breast cancer (BC) is the most commonly diagnosed cancer in women worldwide

  • Results miRNA expression profile of inflammatory breast cancer (IBC), non-inflammatory breast cancer (non-IBC), and healthy controls Among the 12 miRNAs analyzed, 5 miRNAs were differentially expressed in the serum of the 3 groups of subjects (Table 2), using the criteria of at least two-fold differential expression and significance level of < 0.05

  • Regarding the comparison of IBC patient samples to healthy controls we found that only miR-451 was significantly dysregulated (p = 0.019), showing significant down-regulation (15.8-fold) in IBC sera comparison to healthy controls

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Summary

Introduction

Gene expression profiles provide specific molecular signatures containing information which may enable explanation of the mechanisms of tumor development and progression and the poor prognosis observed in IBC. The aim of this study was to identify a molecular signature of IBC based on miRNA profile in serum and to use this profile as an early diagnosis criterion. To this end, we present the first investigation of a panel of miRNA in the serum of inflammatory breast cancer patients and compared this profile to non-inflammatory breast cancer cases and non-cancer controls

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