For individuals diagnosed with locally advanced rectal cancer (LARC), neoadjuvant chemoradiotherapy (CRT) using 5-fluorouracil (5-FU) followed by total mesorectal excision remains the therapeutic standard. Despite its widespread use, a considerable proportion of patients exhibit limited or no response to this treatment, which negatively influences prognosis and exposes them to unnecessary toxicities and surgical postponements. Consequently, the discovery of dependable biomarkers capable of forecasting CRT response has become a pressing clinical objective. Among the microRNAs implicated in colorectal cancer (CRC), microRNA-19b (miR-19b) is known to exert oncogenic effects, modulate sensitivity to 5-FU, and influence patient outcomes. Nevertheless, its relevance in LARC has not been fully explored. In this study, we report that aberrant miR-19b expression is frequent in LARC, and reduced levels of this molecule are significantly correlated with smaller post-CRT tumor size (p = 0.003), lower pathological stage (p = 0.003), and absence of disease recurrence (p = 0.001). Remarkably, diminished miR-19b expression also predicts a more favorable response to neoadjuvant CRT (p < 0.001), along with prolonged overall (p = 0.003) and event-free survival (p = 0.023). Multivariate models identified miR-19b as an independent determinant of both treatment efficacy and clinical outcome, suggesting that this microRNA may serve as a promising prognostic and predictive biomarker for LARC management.
