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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:25
|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.
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页码:1 / 30
页数:30
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