2724 - Predictive Value of Plasma Exosomal miRNAs and mRNAs for Acute Tumor Response in Locally Advanced Cervical Cancer Undergoing Concurrent Chemoradiotherapy

Purpose/Objective(s): Locally advanced cervical cancer (LACC) is primarily managed with weekly cisplatin-based concurrent chemoradiotherapy (CCRT). However, predicting acute tumor response (AR) early during treatment remains a significant clinical challenge. This study aimed to identify plasma exosomal microRNAs (miRNAs) and messenger RNAs (mRNAs) that can serve as early predictive biomarkers for rapid tumor regression in LACC patients undergoing CCRT.

Materials/Methods: A cohort of 41 patients with stage IB–IVB cervical cancer was enrolled. All patients received standardized CCRT, and plasma samples were obtained at two time points: prior to treatment initiation and two weeks after the start of radiation therapy (RT). Exosomal RNA was isolated from plasma, and RNA sequencing was performed to quantify both miRNA and mRNA levels. Acute tumor response was defined as the regression rate of tumor volume (TV) measured at the fourth week of treatment relative to the initial tumor volume (iTV). For each patient, the log2 fold change in RNA expression was calculated by comparing RNA read counts from the two time points. A correlation matrix was then used to identify RNAs significantly associated with AR. The candidate RNAs were further validated using linear regression analysis and Wilcoxon rank-sum tests. Additionally, leave-one-out cross-validation was conducted in subgroups stratified by iTV to assess the robustness of the predictive model.

Results: The analysis identified miR-150-3p, NMT2, and PRDM1 as key biomarkers predictive of AR. A decrease in the levels of these RNAs post-RT was significantly associated with poor tumor regression, especially among patients with larger initial tumor volumes. The predictive model combining these three biomarkers demonstrated a strong correlation with AR in the test dataset (R² = 0.831, P < 0.0001). Validation in an independent cohort also yielded significant results (R² = 0.496, P = 0.006). Cross-validation further confirmed the reliability of these biomarkers across different iTV ranges.

Conclusion: Our study demonstrates that plasma exosomal miR-150-3p, NMT2, and PRDM1 are promising biomarkers for predicting acute tumor response in LACC patients undergoing CCRT. Incorporating these biomarkers into clinical practice may facilitate the development of personalized radiotherapy protocols, potentially leading to enhanced treatment efficacy and improved patient outcomes. Further research involving larger, multicenter cohorts is warranted to validate these findings.