Exploratory Analysis of Circulating miR-486-3p and miR-21-5p in Early Detection and Subtype Classification of Luminal A and B Breast Cancer in Peruvian Women

Abstract

Background

Breast cancer (BC) remains the most common malignancy among women worldwide, and early detection is essential for improving clinical outcomes. There is a growing need for accessible, minimally invasive molecular biomarkers that complement current diagnostic approaches and support molecular subtype classification.

Aims

This exploratory case–control study evaluated the plasma expression of four circulating miRNAs (miR-21-5p, miR-486-3p, miR-451a, and miR-660-5p) in Peruvian women with Luminal A (n = 32) and Luminal B (n = 43) breast cancer and healthy controls (n = 36).

Methods and Results

Expression levels were quantified by qPCR, and diagnostic performance was assessed using logistic regression with leave-one-out cross-validation (LOOCV). miR-486-3p was significantly upregulated in Luminal A compared with both controls and Luminal B, whereas miR-21-5p was downregulated relative to controls. After validation, miR-486-3p retained moderate discriminative ability for distinguishing Luminal A from controls (AUC = 0.651; 95% CI: 0.461–0.841; p = 0.120), while the combined miR-486-3p/miR-21-5p model showed moderate discriminatory performance for differentiating Luminal A from Luminal B (AUC = 0.690; 95% CI: 0.466–0.914; p = 0.0959). Exploratory functional enrichment analyses suggested that experimentally validated targets of these miRNAs were associated with cancer- and immune-related pathways, providing biological context for their potential roles in breast cancer.

Conclusion

These findings provide preliminary evidence supporting the potential of circulating miR-486-3p and miR-21-5p as candidate non-invasive biomarkers for future early detection and molecular subtype classification of Luminal breast cancer. However, these findings should be interpreted cautiously and require validation in larger, independent cohorts before clinical implementation.