Serum MicroRNAs and Tissue EGFR in Triple-Negative Breast Cancer: An Exploratory Case-Control Study miRNA–EGFR in TNBC
Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype for which reliable molecular biomarkers remain an important research need. We aimed to compare serum miR-21, miR-30, and miR-125 expression and tissue EGFR mRNA expression between TNBC cases and their respective control groups, and to explore biomarker correlations and apparent diagnostic discrimination.
Methods: This hospital-based case-control study was conducted from April 2024 to November 2025. Among 105 women with histopathologically confirmed HER2-negative breast cancer, 32 patients with TNBC underwent molecular analysis. Serum miRNAs were compared with healthy female controls, whereas tumor-tissue EGFR mRNA was compared with histopathologically confirmed benign breast tissue because healthy breast tissue could not be obtained ethically. Expression was measured by reverse-transcription quantitative polymerase chain reaction. Group comparisons used ΔCt values; receiver operating characteristic (ROC) analyses used 2−ΔΔCt values and were exploratory and unvalidated.
Results: Relative to their respective control groups, TNBC cases had higher miR-21 (4.30-fold) and tissue EGFR (6.69-fold) expression and lower miR-30 (0.02-fold) and miR-125 (0.13-fold) expression (all P < .001). In exploratory analyses restricted to TNBC participants, serum miR-30 and miR-125 were positively correlated (r = 0.601, P < .001, n = 30), meeting the Bonferroni-adjusted threshold; all other correlations were weak and nonsignificant. Apparent AUCs were 0.876 for miR-21, 1.000 for miR-30, 1.000 for miR-125, and 0.865 for EGFR; assay-specific ROC sample sizes ranged from 44 to 47 participants.
Conclusion: Serum miRNA and tissue EGFR expression differed between TNBC cases and their distinct comparator groups. The markers were measured in different biological compartments, the cohort was small, reference genes were not validated for stability, and the ROC results were not validated internally or externally. Therefore, these results are exploratory and do not establish a combined clinical biomarker panel.
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Copyright (c) 2026 Sahar M. Hussein, Ruaa Maan Attallah , Noora A. Hadi, Roya Hadi Al-Haddad
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