Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

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.

Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

“…We have recently discovered differentially expressed miRNAs in IBC tumors relative to non-IBC as tissue biomarkers, using human breast cancer miRNA PCR array [ 34 ]. To extend our findings and to identify sEV-derived miRNAs as non-invasive blood-based biomarkers for IBC, we selected five miRNAs (miR-19a, miR-129-5p, miR-181b-5p, miR-222-3p, and let-7a-5p).…”

MicroRNAs Involved in Inflammatory Breast Cancer: Oncogene and Tumor Suppressors with Possible Targets

“…No significant differences were observed in terms of alterations in the expression of miR-1-3p in IBC compared with non-IBC tumors; however, Atef Fahim et al (2020) found a decreasing trend in expression levels of miR-1-3p in IBC versus non-IBC, which was consistent with the previous studies presenting in vitro and in vivo evidence on the function of miR-1 as a tumor suppressor and the association between its reduced expression with a short general rate of survival among patients with breast cancer. This may be due to the downregulation of miR-1 in breast cancer tissues versus normal ones, as well as its re-expression suppressing tumor cell growth, migration, and metastasis, and enhancing apoptosis in vitro and in vivo through targeting K-RAS and human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) (Liu et al, 2015a).…”

“…As Fahim et al (2020) suggested, the upregulation of miR-181c-5p and miR-181b-5p has been revealed from data obtained through miRNA PCR array and qPCR, respectively. This result is consistent with a previous study demonstrating an elevated level of miR-181c in IBC compared with nontumor tissues.…”

“…The latter is related to the attenuated characteristics of breast CSCs through targeting the stemness master regulator DNp63 (i.e., p63 lacking the N-terminal transactivation domain) (DeCastro et al, 2013). However, it is worth noting that miR-203 has been found to play an oncogenic role in the ER+ MCF-7 breast cancer cells (He et al, 2016), as well as in ovarian cancer, indicating the functions being conditioned on cell/tumor entity as well as oncogenic state environment (Fahim et al, 2020).…”

Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer

“…It is important to note that the combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the accuracy of this differentiation. These results indicate that the combination of miR-181b-5p, miR-200b-3p, miR-200c-3p, and miR-1-3p may be promising diagnostic biomarkers for patients with inflammatory breast cancer [ 55 ]. However, their findings should be verified comprehensively in a prospective large cohort of patients with inflammatory breast cancer, and their roles as therapeutic targets should be further examined.…”