Cho Oyeon
Gynecologic Cancer Center, Department of Radiation Oncology, Ajou University School of Medicine 164 World Cup-ro, Yeongtong-gu, Suwon 16499, Korea.
Am J Cancer Res. 2025 Feb 15;15(2):546-558. doi: 10.62347/SPQY5709. eCollection 2025.
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) (cm) measured at the fourth week of treatment compared with the initial TV (iTV). The log 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, , and 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, , and showed strong correlation with AR (R = 0.831, < 0.0001) in the test dataset and was validated in an independent cohort (R = 0.496, = 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, , and 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.
局部晚期宫颈癌（LACC）主要采用以顺铂为基础的每周同步放化疗（CCRT）进行治疗；然而，预测急性肿瘤反应仍然具有挑战性。本研究旨在鉴定可预测接受CCRT的LACC患者肿瘤快速消退的血浆外泌体微小RNA（miRNA）和信使RNA（mRNA）。总体而言，纳入了41例IB-IVB期宫颈癌患者。所有患者均接受CCRT，并在治疗前和放疗（RT）后2周收集血浆外泌体RNA样本。急性肿瘤反应（AR）定义为治疗第四周时测量的肿瘤体积（TV）（cm）与初始TV（iTV）相比的消退率。通过比较每位患者CCRT第二周前后的RNA读数计算miRNA和mRNA的对数倍变化。相关矩阵确定了与AR相关的RNA。所选RNA通过线性回归和Wilcoxon秩和检验进行验证。基于iTV在亚组中进行留一法交叉验证。miR-150-3p等被鉴定为AR的关键预测因子，显示出与免疫介导的肿瘤反应有显著关联。这些RNA放疗后水平的降低与不良AR显著相关，尤其是在iTV较大的患者中。结合miR-150-3p等的预测模型在测试数据集中与AR显示出强相关性（R = 0.831，P < 0.0001），并在独立队列中得到验证（R = 0.496，P = 0.006）。交叉验证表明这些生物标志物在预测不同TV的AR方面具有稳健性。这些发现突出了血浆外泌体miR-150-3p等在预测接受CCRT的LACC患者AR方面的潜力，是有前景的生物标志物。这些发现有助于制定个性化放疗策略并改善患者预后。有必要进行进一步的多中心研究，在更大、更多样化的队列中验证这些生物标志物。
