Circulating microRNAs as prognostic biomarkers in patients with oropharyngeal cancer undergoing radiotherapy: temporal dynamics analysis

The incidence of oropharyngeal cancer (OPC) is increasing. Thus, there is a need for biomarkers that can identify high-risk patients and support personalised treatment. This study investigated the prognostic significance of circulating microRNAs (miRNAs) for progression-free survival (PFS) and overall survival (OS) in patients with OPC undergoing radiotherapy (RT). The expression of 20 circulating miRNAs was analysed in serum samples collected both before and after RT as a possible prognostic marker in patients treated for OPC. We analysed 80 patients with OPC treated with curative-intent RT. The median PFS was 42.9 months (95%CI: 25.6 - not reached), and the median OS was 63.7 months (95%CI: 33.9 - not reached). In univariate analysis, higher pre-treatment levels of miR-21-5p (HR: 2.12, 95%CI: 1.34-3.36) and miR-148a-3p (HR: 1.38, 95%CI: 1.03-1.85), as well as lower post-treatment levels of miR-345-5p (HR: 0.61, 95%CI: 0.41-0.90), were associated with worse survival. These associations remained significant in multivariable analysis adjusted for clinical factors. A combined risk model based on pre-RT miR-21-5p and post-RT miR-345-5p identified a high-risk group with significantly shorter PFS (HR: 3.01, 95%CI: 1.27-7.14) and OS (HR: 3.19, 95%CI: 1.25-8.15) compared with the low-risk group. High pre-RT hsa-miR-21-5p and low post-RT hsa-miR-345-5p were both independently associated with inferior PFS and OS. These results support the clinical relevance of integrating dynamic miRNA profiling into risk-stratification frameworks and may potentially inform more personalised strategies for post-RT monitoring in OPC patients.