The Role of miRNAs in the Prognosis of Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

Breast cancer is one of the most common malignancies among women around the world. The basal or triple-negative subtype (TNBC) is a heterogeneous group of tumors, characterized by its aggressive and metastatic nature, with low survival and worse prognosis. Research on genetic biomarkers, such as microRNAs (miRs) in TNBC, demonstrate their relevance in the prognosis of the disease. Therefore, the objective of this research was to verify the role of miRs in the prognosis of TNBC. A search was carried out in the PubMed (MEDLINE), Web of Science, and Scopus databases, with articles in the English language from 2010 to 2022. Only articles that analyzed the role of miRNAs in the prognosis of TNBC and that met the criteria of the MOOSE method were included. For the preparation and planning of this systematic review, a PRISMA checklist and the MOOSE method were used. The Newcastle–Ottawa Scale was used to analyze the quality of the included studies. The excluded criteria considered were: (1) studies that presented duplication in the databases; (2) reviews of the literature, clinical case reports, meta-analyses, conference abstracts, letters to the editor, theses, dissertations, and book chapters; (3) studies that stratified only women diagnosed with other subtypes of breast cancer subtypes; (4) experiments without a control or comparison group. After the bibliographic survey of the 2.274 articles found, 43 articles met the inclusion criteria, totaling 5421 patients with TNBC analyzed for this review. Six miRs (miR-155, miR-21, miR-27a/b/, miR-374a/b, miR-30a/c/e, and miR-301a) were included in the meta-analysis. A low expression of miR-155 was associated with reduced overall survival (OS) (HR: 0.68, 95% CI: 0.58–0.81). A high expression of miR-21 was a predictor of OS reduction (HR: 2.56; 95% CI: 1.49–4.40). In addition, high levels of miR-27a/b and miR-301a/b were associated with lower OS, while the decreased expression levels of miR-30 and miR-374a/b were associated with worse relapse-free survival (RFS) and shorter disease-free survival (DFS), respectively. The present study revealed that miRs play essential roles in the development of metastases, in addition to acting as suppressors of the disease, thus improving the prognosis of TNBC. However, the clinical application of these findings has not yet been investigated.