Published online Apr 24, 2026. doi: 10.5306/wjco.v17.i4.115287
Revised: November 19, 2025
Accepted: March 2, 2026
Published online: April 24, 2026
Processing time: 190 Days and 14 Hours
The biological heterogeneity of breast cancer requires robust biomarkers to guide therapy. MicroRNAs (miRNAs) are pivotal post-transcriptional regulators, yet their longitudinal dynamics in matched tissue and plasma during neoadjuvant chemotherapy (NACT) remain poorly defined.
To evaluate the prognostic and predictive value of a panel of tumor-suppressive (miR-34a, -124a, -137) and oncogenic (miR-155, -373) miRNAs pre- and post-NACT.
We performed longitudinal profiling of five miRNAs in matched tumor and plasma from 38 patients [27 hormone receptor (HR)-positive; 11 HR-negative]. The study integrated matched tissue-plasma sampling, HR-stratified evaluation, and long-term survival follow-up. Prognostic associations were assessed via multivariate Cox regression, adjusting for age, HR status, and Ki-67.
High baseline miR-34a and miR-373 independently predicted improved overall survival (P < 0.001). miR-137 was the only miRNA significantly associated with pathological response, showing increased expression in good responders (P = 0.048). While clinical factors, such as older age and HR-positive status, correlated with favorable outcomes, elevated Ki-67 predicted worse overall survival (P = 0.003). NACT significantly modulated profiles, including a shift of miR-124a toward G2 tumors (P = 0.041). Notably, the prognostic value of baseline miRNAs diminished post-treatment, reflecting a convergence of miRNA expression patterns and unstable risk estimates in the post-NACT setting.
Baseline miR-34a and miR-373 are potent prognostic markers, while miR-137 predicts chemosensitivity. Treatment-induced remodeling diminishes the prognostic clarity of post-NACT miRNA landscapes.
Core Tip: This longitudinal study profiles matched tumor and plasma microRNAs dynamics in breast cancer patients before and after neoadjuvant chemotherapy. By integrating tissue-plasma signatures with survival data, stratified by hormone receptor status, we identified miR-34a and miR-373as independent prognostic markers at diagnosis. Furthermore, miR-137 was identified as candidate predictor of chemosensitivity. Our findings reveal that chemotherapy induces significant “molecular remodeling” and expression convergence across the cohort, which diminishes the prognostic clarity of markers post-treatment. Consequently, our data suggest that baseline profiling offers superior prognostic utility. These findings underscore the critical role of temporal context in microRNA-guided precision oncology and highlight the intricate interplay between systemic and intratumoral molecular landscapes.