Plasma exosomal miR-150-3p, NMT2, and PRDM1 as predictive biomarkers of acute tumor response in patients with cervical cancer undergoing chemoradiotherapy.

Abstract

Locally advanced cervical cancer (LACC) is primarily treated with weekly cisplatin-based concurrent chemoradiotherapy (CCRT); however, predicting acute tumor response remains challenging. This study aimed to identify plasma exosomal microRNAs (miRNAs) and messenger RNAs (mRNAs) that could predict rapid tumor regression in patients with LACC undergoing CCRT. Overall, 41 patients with stage IB-IVB cervical cancer were included. All patients received CCRT, and plasma exosomal RNA samples were collected before treatment and 2 weeks after radiation therapy (RT). Acute tumor response (AR) was defined as the regression rate of tumor volume (TV) (cm³) measured at the fourth week of treatment compared with the initial TV (iTV). The log₂ fold change of miRNA and mRNA was calculated by comparing RNA read counts before and after the second week of CCRT for each patient. A correlation matrix identified RNAs associated with AR. The selected RNAs were validated through linear regression and Wilcoxon rank-sum tests. Leave-one-out cross-validation was performed in subgroups based on iTV. miR-150-3p, NMT2, and PRDM1 were identified as key predictors of AR, demonstrating significant associations with immune-mediated tumor responses. A decrease in post-RT levels of these RNAs was significantly associated with poor AR, particularly in patients with large iTVs. The predictive model combining miR-150-3p, NMT2, and PRDM1 showed strong correlation with AR (R² = 0.831, P < 0.0001) in the test dataset and was validated in an independent cohort (R² = 0.496, P = 0.006). Cross-validation indicated the robustness of these biomarkers in predicting AR across varying TVs. These findings highlight the potential of plasma exosomal miR-150-3p, NMT2, and PRDM1 are promising biomarkers for predicting AR in patients with LACC undergoing CCRT. These findings could facilitate personalized RT strategies and improve patient outcomes. Further multicenter studies are warranted to validate these biomarkers in larger, diverse cohorts.