Abstract
Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.
Highlights
Breast cancer is the most frequent cancer in women, with over two million new cases in 2018 [1]
Using the online platform STRING, which uses three different databases: Gene Ontology (GO), Protein families (Pfam), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to predict protein-protein interaction (PPI) networks [22], we developed a single network of all differentially expressed genes (DEGs), including the candidate genes targeted by differentially upand downregulated miRNAs
We identified in this study a panel of differentially expressed miRNAs and detected an upregulation of one the downstream targets, zinc finger E box-binding homeobox 2 (ZEB2), in carcinoma tissues of Inflammatory breast cancer (IBC) vs. non-IBC
Summary
Breast cancer is the most frequent cancer in women, with over two million new cases in 2018 [1] It ranks as the fifth cause of cancer-related death, with 627,000 cases in 2018. Inflammatory breast cancer (IBC) is a rare but the most aggressive variant of breast cancer that has a rapid progression from the onset of disease [2]. It is clinically characterized by edema, redness, and dimpling of the skin (peau d’orange) caused by tumor emboli blocking dermal lymphatics [3]. Several studies have been conducted to discover new diagnostic and predictive biomarkers [7,8,9,10], IBC is still misdiagnosed due to the lack of accurate and reliable molecular biomarkers
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