Plasma-derived Exosomal miR-25-3p and miR-23b-3p as Predictors of Response to Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

Background: Exosomal miRNAs have emerged as promising biomarkers for cancer. However, little is known about the role of exosomal miRNAs in the response prediction of esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy (CRT).

Methods: In this prospective study, 40 ESCC patients treated by CRT were enrolled from January 2021 to June 2022. Exosomes were isolated from plasma through EXODUS platform. We used small RNA sequencing in 14 samples of ESCC patients (7 responders, 7 non-responders) and the selected exosomal miRNAs were further validated in the extended cohort of 40 ESCC patients by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: In the discovery phase, we identified five significantly differentially expressed exosomal miRNAs from miRNA sequencing data between the responder and non-responder patients. In the extended groups of responders (n = 27) and non-responders (n = 13), only miR-23b-3p (= 0.035, AUC = 0.708) and miR-25-3p (< 0.001, AUC = 0.932) were confirmed to have the predictive ability to distinguish non-responders from responders. The patients with low levels of miR-25-3p had a significantly shorter progression-free survival (PFS) than those with high levels (= 0.035). Multivariate Cox regression analysis revealed that miR-25-3p may serve as an independent predictive biomarker of PFS in ESCC patients received CRT.

Conclusion: Exosomal miR-25-3p and miR-23b-3p serve as promising biomarkers for predicting the early effectiveness of CRT in locally advanced ESCC patients, whereas miR-25-3p is a novel prognostic marker for ESCC. However, further larger prospective studies are needed to confirm their utility for individualized treatment decision in ESCC.