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Relevance of the MicroRNA (Mirna) Processor DICER Expression in the Biological Behaviour and Pathological Response of Nigerian Breast Cancer Tissues
Abstract
Background: Breast cancer (BC) among Nigerians is characterised by high grade, triple negative, basal-like phenotype tumours with high proliferation indices and poor prognosis. The loss of Dicer expression has been speculated to play a key role in BC with similar features among the women in the Western countries.
Objectives: To demonstrate the role of the Dicer expression in relation to pathological response in BC, in order to determine the biological behaviour and its prognostic significance in BC among Nigerian women using immunohistochemistry and Tissue microarray (TMA).
Methods: This study investigated the immune profiles of the Dicer in 241 tissue microarray of breast cancer tissue of Nigerian women and correlated the protein expression with the pathological response and the other biomarker expressions to determine the functional significance in Nigerian women.
Results: Protein expression of Dicer as compared with other biomarkers expression showed there was significant association between the loss of Dicer expression and the down-regulators of Breast Cancer Associated Gene-1 (BRCA1), metastasis tumour antigen-1(MTA 1) (p = 0.004), Inhibitor differentiation-4 (ID4) (p = 0.002), ubiquitin conjugating enzyme-9 (UBC9) (p = 0.008) and protein inhibitor of activated signal transducer gamma PIASγ (p = 0.002). Other relevant Homologous repair pathway markers included poly (ADP-ribose) polymerase-1(PARP1) (p < 0.001) and RAD51 (p < 0.001), cell cycle regulator protein-27(p27) (p = 0.024), the proliferation kinetic protein ( Ki-67) (p = 0.003) and epidermal growth factor receptor (EGFR) expression (p = 0.013). Survival analysis also showed that there was no significant correlation between tumours negative for Dicer and patient outcome.
Conclusion: This study demonstrated that the loss of Dicer is associated with intermediate to higher grade tumour, discrepant MI/Ki-67 expression, p27 loss, homologous recombination response dysregulation, high EGFR and Ki-67 expression. Therefore, Dicer expression appears to play a major role in the biology of BC among Nigerian women. A targeted therapy on Dicer expression would enhance the management of BC among Nigerian women.
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References
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A publication of the Medical and Dental Consultants Association of Nigeria, Olabisi Onabanjo University Teaching Hospital, (OOUTH) Sagamu Branch, Nigeria