Circulating Plasma miRNA-548L as Novel Predictive Biomarker of Radiotherapy-Induced Severe Oral Mucositis in Patients...

Background/Objectives: Oral mucositis (OM) is a common complication in laryngeal cancer (LC), during radiotherapy (RT), significantly affecting patient outcomes. Identifying sensitive biomarkers to predict OM severity is therefore crucial. MicroRNAs, which regulate inflammatory pathways involved in OM, are promising candidates. This retrospective study aimed to evaluate plasma miRNA-548L as a predictive biomarker for the occurrence and severity of OM in LC patients undergoing RT. Methods: The expression levels of the selected miRNAs were analyzed in plasma samples obtained from 76 LC patients prior to the initiation of RT. Bioinformatics analyses were performed to identify molecular pathways regulated by miRNA-548L and their potential link to the pathogenesis of OM. Results: Significantly decreased levels of the studied miRNA were observed in the plasma of LC patients who developed severe OM after the IV^th (p < 0.001), V^th (p = 0.039), VI^th (p < 0.001), and VII^th (p < 0.001) cycles of RT. Additionally, the expression of miRNA-548L enabled reliable differentiation between patients who developed severe OM during the IV^th (AUC = 0.81, p < 0.001), V^th (AUC = 0.77, p < 0.001), VI^th (AUC = 0.82, p < 0.001), and VII^th (AUC = 0.86, p < 0.001) weeks of treatment. Importantly, lower expression of miRNA-548L (HR = 3.12; p = 0.010) was significantly associated with shorter median overall survival (OS). Conclusions: Pretreatment plasma miRNA-548L shows potential as a biomarker for predicting severe OM in LC patients undergoing RT. Notably, reduced miRNA-548L expression is associated with shorter OS and may help stratify patients by OM severity.