MicroRNAs miR-142-5p, miR-150-5p, miR-320a-3p, and miR-4433b-5p in Serum and Tissue: Potential Biomarkers in Sporadic Breast Cancer

Tamyres Mingorance Carvalho; Guillermo Ortiz Brasil; Tayana Schultz Jucoski; Douglas Adamoski; Rubens Silveira de Lima; Cleverton C Spautz; Karina Furlan Anselmi; Patricia Midori Murobushi Ozawa; Iglenir João Cavalli; Jaqueline Carvalho de Oliveira; Daniela Fiori Gradia; Enilze Maria de Souza Fonseca Ribeiro

doi:10.3389/fgene.2022.865472

MicroRNAs miR-142-5p, miR-150-5p, miR-320a-3p, and miR-4433b-5p in Serum and Tissue: Potential Biomarkers in Sporadic Breast Cancer

Front Genet. 2022 Jun 30:13:865472. doi: 10.3389/fgene.2022.865472. eCollection 2022.

Authors

Affiliations

¹ Laboratory of Human Cytogenetics and Oncogenetics, Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba, Brazil.
² Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), Sao Paulo, Brazil.
³ Breast Disease Center, Hospital Nossa Senhora das Graças, Curitiba, Brazil.
⁴ Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, United States.

Abstract

Breast cancer (BC) is a heterogeneous disease, and establishing biomarkers is essential to patient management. We previously described that extracellular vesicle-derived miRNAs (EV-miRNAs) miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p in serum discriminated BC from control samples, either alone or combined in a panel. Using these previously described markers, we intend to evaluate whether the same markers identified in EVs are also potential biomarkers in tissue and serum. Expression analysis using RT-qPCR was performed using serum of 67 breast cancer patients (BC-S), 19 serum controls (CT), 83 fresh tumor tissues (BC-T), and 29 adjacent nontumor tissue samples (NT). In addition, analysis from The Cancer Genome Atlas (TCGA) data (832 BC-T and 136 NT) was performed. In all comparisons, we found concordant high expression levels of miR-320a and miR-4433b-5p in BC-S compared to CT in both EVs and cell-free miRNAs (cf-miRNAs). Although miR-150-5p and miR-142-5p were not found to be differentially expressed in serum, panels including these miRNAs improved sensitivity and specificity, supporting our previous findings in EVs. Fresh tissue and data from the TCGA database had, in most comparisons, an opposite behavior when compared to serum and EVs: lower levels of all miRNAs in BC-T than those in NT samples. TCGA analyses revealed reduced expression levels of miR-150-5p and miR-320a-3p in BC-T than those in NT samples and the overexpression of miR-142-5p in BC-T, unlike our RT-qPCR results from tissue in the Brazilian cohort. The fresh tissue analysis showed that all miRNAs individually could discriminate between BC-T and NT in the Brazilian cohort, with high sensitivity and sensibility. Furthermore, combining panels showed higher AUC values and improved sensitivity and specificity. In addition, lower levels of miR-320a-3p in serum were associated with poor overall survival in BC Brazilian patients. In summary, we observed that miR-320a and miR-4433b-5p distinguished BC from controls with high specificity and sensibility, regardless of the sample source. In addition, lower levels of miR-150-5p and higher levels of miR-142-5p were statistically significant biomarkers in tissue, according to TCGA. When combined in panels, all combinations could distinguish BC patients from controls. These results highlight a potential application of these miRNAs as BC biomarkers.

Keywords: biomarkers; breast cancer; miR-142-5p; miR-150-5p; miR-320a; miR-4433b-5p.