Serum microRNAs and Tissue EGFR in Triple-Negative Breast Cancer: An Exploratory Case-Control Study
Abstract
Background: Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype for which reliable molecular biomarkers remain an important research need. Objective is 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 (4.06-fold) and tissue EGFR (6.92-fold) expression and lower miR-30 (0.22-fold) and miR-125 (0.29-fold) expression (all p < 0.001). The inverse miR-21/miR-125 correlation was nominally significant (r = −0.316, p = 0.035) but did not meet the Bonferroni-adjusted threshold for six comparisons. 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 sample sizes ranged from 43 to 47 participants.
Conclusion: Serum miRNA and tissue EGFR expression differed between TNBC cases and their distinct comparator groups. Because the markers were measured in different biological compartments, the cohort was small, reference-gene stability was not validated, and ROC performance was not internally or externally validated, 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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