Circulating miRNA Signatures as Prognostic Biomarkers in Breast Cancer: A Comprehensive Analysis of Expression Profiles, Functional Targets, and Survival Correlations
Abstract
Purpose: Circulating microRNAs have emerged as promising non-invasive biomarkers for oncology; however, comprehensive frameworks linking their differential expression in the serum to downstream functional networks and clinical outcomes in early-stage breast carcinoma remain limited. To systematically identify and functionally characterize circulating microRNA signatures with diagnostic and prognostic utility in early-stage breast carcinoma by integrating large-scale transcriptomic datasets.
Methods: A secondary bioinformatic analysis was conducted using serum microRNA microarray data (GSE73002) comprising 1,270 patients with early-stage breast carcinoma and 2,686 healthy controls. Differential expression was quantified using the limma empirical Bayes method. Putative targets of the most deregulated microRNAs were predicted via miRWalk, followed by functional enrichment analysis. Prognostic significance was independently validated using The Cancer Genome Atlas (TCGA) survival data.
Results: Differential expression analysis identified 1,450 upregulated and 898 downregulated miRNAs (FDR < 0.05). Functional enrichment of the predicted targets of top upregulated miRNAs (e.g., hsa-miR-614 and hsa-miR-4532) demonstrated convergence on pathways governing chromatin remodeling (targeting KMT2D and SUV39H1), transcriptional regulation, and RNA metabolism. Independent survival modeling revealed that elevated expression of hsa-miR-614 was significantly associated with diminished overall survival (HR =, 2.81; 95% CI, 1.24–6.39; P = 0.0098)..
Conclusion: Early breast tumorigenesis is characterized by the systemic dysregulation of circulating microRNAs that govern epigenetic and transcriptional networks. These specific signatures, notably hsa-miR-614, offer robust potential as liquid biopsy-based diagnostic and prognostic biomarkers for clinical stratification.
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Authors
Copyright (c) 2026 Adam Neama Al-ebadi, Rasha Abd Ali Al-khalidi
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright©. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International License, which permits copy and redistribution of the material in any medium or format or adapt, remix, transform, and build upon the material for any purpose, except for commercial purposes.