Clinical Translatability of “Identified” Circulating miRNAs for Diagnosing Breast Cancer: Overview and Update

Abstract

The effective management of patients with breast cancer (BC) depends on the early diagnosis of the disease. Currently, BC diagnosis is based on diagnostic imaging and biopsy, while the use of non-invasive circulating biomarkers for diagnosis remains an unmet need. Among the plethora of proposed non-invasive biomarkers, circulating microRNAs (miRNAs) have been considered promising diagnostic molecules because they are very stable in biological fluids and easily detectable. Although the discovery of miRNAs has opened a new avenue for their clinical application, the clinical translatability of these molecules remains unclear. This review analyses the role of circulating miRNAs as BC diagnostic biomarkers and focuses on two essential requirements to evaluate their clinical validity: i) Specificity and ii) consistent expression between the blood and tissue. These two issues were analyzed in depth using the Human miRNA Disease Database (HMDD v3.0) and the free search engine PubMed. One hundred and sixty three BC-associated miRNAs were selected and analyzed for their specificity among all human pathologies that shared deregulation (291) and consistent expression in the bloodstream and the tissue. In addition, we provide an overview of the current clinical trials examining miRNAs in BC. In conclusion, we highlight pitfalls in the translatability of circulating miRNAs into clinical practice due to the lack of specificity and a consistent expression pattern between the tissue and blood.

Prognostic and Clinicopathological Significance of MiR-155 in Breast Cancer: A Systematic Review

“…As reported in Figure 2, 14% of selected studies reported miR-155 as a tissue-deregulated miRNA associated with BC, whereas 3% of studies associated its circulating deregulation with BC. Although the non-specificity of miR-155 in human cancers was previously found in our study [7], the highest number of studies associating miR-155 with BC (14%) suggests its potential role as a tissue biomarker. However, circulating miR-155 seems to have a better role as a biomarker of pancreatic cancer (26%) than of BC (3%).…”

“…MiRNAs are useful tools for diagnostic and prognostic purposes in several diseases [40]. In recent years, many studies have investigated the clinical value of miRNAs in BC [7,41], a worldwide public health problem that poses significant challenges in terms of disease management. To date, miR-155 represents one of the most studied miRNAs in different human pathologies, including BC.…”

“…To date, miRNA biomarkers are not currently used in clinical practice, because their translation from the lab into validated diagnostic tests represents a major challenge. Among the miRNAs found to be deregulated in BC, miR-21 and miR-155 have been identified as the most frequently BC-associated, although they are the most non-specific for diagnostic purposes [7]. Moreover, a recent meta-analysis has reported that miR-21 has a strongly predictive role and may be applied as a general prognostic marker of BC [8].…”

Circulating miRNAs in HER2-Positive and Triple Negative Breast Cancers: Potential Biomarkers and Therapeutic Targets

“…On the other hand, several recent studies have shown that microRNAs (miRNAs) can provide a potential diagnostic and therapeutic approach for human breast cancers including estrogen-receptor negative breast cancers [34][35][36]. Moreover, circulating miRNAs can be used as a non-invasive tool for early diagnosis and provide a new avenue for estrogen-receptor negative breast cancer management [37]. In this review we will summarize the recent advances made in the identification and role of estrogen-receptor negative specific circulating miRNAs.…”

<p>Mirna21 Expression in the Breast Cancer Tumor Tissue is Independent of Neoadjuvant Chemotherapy</p>

“…However, miRNAs have not been applied in clinical practice because of inconsistencies in the selection of specific miRNAs for diagnostic and prognostic purposes, methodological challenges, patient heterogeneity, and differences in genetic background, sex, age and metabolic status. 9 miRNA-21 has been described as one of the most significantly upregulated miRNAs in human breast cancer and other neoplasms, such as gastric, colorectal, pancreatic, lung and ovarian carcinomas. [10][11][12] In addition, its expression has been associated with tumor diagnosis and development as well as poor prognosis.…”