Micro-RNAs (miRs) are post-transcriptional regulators of gene expression involved in several important biological processes. BRCA1 is a tumor suppressor gene and BRCA1-silent breast cancers (BC) tend to be more aggressive.
BRCA1 and microRNAs 7, 10b, 205ab, 218a expression as prognostic markers in primary breast cancers – a
retrospective cohort study.
Cesar A. S. T. Vilanova-Costa1,2, Jéssica E. P. Ramos3, Juliana F. Paes4, Daniel R. Bastos1, Nathália A. Nogueira1,4, Silvia H.
Rabelo-Santos6, Raphael B. Parmigiani7, Vera A. Saddi1,3,4,5*
1Laboratório de Genética e Biodiversidade, Programa de Pós-graduação em Ciências Ambientais e Saúde, Universidade
Católica de Goiás, Goiânia, Goiás, Brazil.
2Laboratório de Biologia Tumoral, Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás, Goiânia, Goiás,
Brazil.
3Escola de Ciências Médicas, Farmacêuticas e Biomédicas, Pontifícia Universidade Católica de Goiás, Goiânia, Goiás, Brazil.
4Programa de Pós-graduação em Ciências da Saúde, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
5Laboratório de Oncogenética e Radiobiologia, Instituto de Ensino e Pesquisa, Associação de Combate ao Câncer em Goiás,
Goiânia, Goiás, Brazil.
6Instituto de Patologia Tropical, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
7Idengene Medicina Diagnóstica, São Paulo, São Paulo, Brazil.
Micro-RNAs (miRs) are post-transcriptional regulators of gene expression involved in several important biological processes.
BRCA1 is a tumor suppressor gene and BRCA1-silent breast cancers (BC) tend to be more aggressive. Since BRCA1 may be
regulated at post-transcriptional level by miRNAs, the purpose of this study was to evaluate the prognostic value of human
miR-7, miR-10b, miR-205ab and miR-218b and BRCA1 expression levels in BC. A set of 36 triple-negative (TN) and 56 nontriple-
negative (NTN) breast tumors was analyzed. Total miRNA was extracted from formalin-fixed paraffin-embedded
(FFPE) BCs collected from the Pathology Department of Araújo Jorge Hospital-ACCG (Goiânia, Goiás, Brazil). MiRs
expression was quantified by Quantitative Real-Time PCR (qRT-PCR) and BRCA1 expression was evaluated by
immunohistochemistry (IHC). The present study was approved by the institutional Ethics Committee of Araújo Jorge Hospital
(Report n° 948.930, 2015). The relative expression levels of miRs and clinic pathological features of breast cancers were
compared. Overall survival in 60 months was 72.8%, and it was influenced by TNBC phenotype (p=0.044), tumor size
(p=0.007), lymph node involvement (p=0.038), distant metastasis (p=0.0008), BRCA1 negative expression (0.039), miR-7
(p=0.026) and miR-10b (p=0.011) overexpression. MicroRNA hsa-miR-7 overexpression was associated with larger tumors
(>2 cm) (p=0.041), higher histological grade (p=0.028), TN phenotype (p=0.012), BRCA1-negative expression (p=0.047) and
worse survival (p=0.026). Overexpression of hsa-miR-10b was associated with larger tumors (p=0.047), lymph node (p=0.032)
and distant metastases (0.019), higher histological grade (p=0.009), TN phenotype (p=0.027), BRCA1-negative expression
(p=0.006) and worse survival (p=0.011). Meanwhile, underexpression of hsa-miR-205ab was associated with larger tumors
(p=0.027), lymph node (p=0.046) and distant metastases (p=0.014), BRCA1-negative expression (p=0.027), TN phenotype
(p=0.038) and worse survival (p=0.024). While, hsa-miR-218a underexpression was associated with a larger tumor size
(p=0.032), lymph node (p=0.011) and distant metastases (p=0.022), TN phenotype (p=0.019), negative expression of BRCA1
(p=0.039) and worse survival (p=0.003). Our results show that BRCA1 protein expression assessment, miR-7 and miR-10b
overexpression and miR-205ab and miR-218b underexpression could be useful in evaluating BCs prognosis, especially for
patients with triple negative tumors.
Keywords: BRCA1; micro-RNA; hsa-miR-7; hsa-miR-10b; hsa-miR-205ab; hsa-miR-218b; triple-negative breast cancer.