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

被引:29
作者
Fahim, Sarah Atef [1 ]
Abdullah, Mahmoud Salah [2 ]
Espinoza-Sanchez, Nancy A. [3 ]
Hassan, Hebatallah [4 ]
Ibrahim, Ayman M. [4 ]
Ahmed, Sarah Hamdy [2 ]
Shakir, George [2 ,5 ]
Badawy, Mohamed A. [6 ]
Zakhary, Nadia, I [7 ]
Greve, Burkhard [8 ]
El-Shinawi, Mohamed [9 ]
Gotte, Martin [3 ]
Ibrahim, Sherif Abdelaziz [4 ]
机构
[1] Cairo Univ, Fac Sci, Chem Dept, Biochem Program, Giza 12613, Egypt
[2] Cairo Univ, Fac Sci, Chem Dept, Biotechnol Biomol Chem Program, Giza 12613, Egypt
[3] Munster Univ Hosp, Dept Gynecol & Obstet, D-48149 Munster, Germany
[4] Cairo Univ, Fac Sci, Dept Zool, Giza 12613, Egypt
[5] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent, D-80539 Munich, Germany
[6] Cairo Univ, Fac Sci, Chem Dept, Giza 12613, Egypt
[7] Cairo Univ, Natl Canc Inst, Canc Biol Dept, Cairo 11796, Egypt
[8] Univ Hosp Munster, Dept Radiotherapy Radiooncol, D-48149 Munster, Germany
[9] Ain Shams Univ, Fac Med, Dept Gen Surg, Cairo 11566, Egypt
关键词
inflammatory breast cancer; microRNAs; miR-181b-5p; miR-200b-3p; miR-200c-3p; miR-203a-3p; miR-1-3p; ZEB2; hub genes; EPITHELIAL-MESENCHYMAL TRANSITION; THERAPEUTIC TARGETS; REPRESSORS ZEB1; CELL-MIGRATION; CANCER-CELLS; FAMILY; PROLIFERATION; SURVIVAL; MIR-1; METASTASIS;
D O I
10.3390/biom10071059
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页码:1 / 30
页数:30
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