Identifying adipocyte-derived exosomal miRNAs as potential novel prognostic markers for radiotherapy of esophageal squamous cell carcinoma  

作　　者：Yang-Yang Ge Xiao-Chun Xia An-Qing Wu Chen-Ying Ma Ling-Hui Yu Ju-Ying Zhou 

机构地区：[1]Department of Radiation Oncology,The First Affiliated Hospital of Soochow University,Suzhou 215006,Jiangsu Province,China [2]Department of Radiotherapy,The Affiliated Tumor Hospital of Nantong University,Nantong 226361,Jiangsu Province,China [3]School of Radiation Medicine and Protection,Soochow University,Suzhou 215123,Jiangsu Province,China [4]Department of Brachytherapy,The Affiliated Tumor Hospital of Nantong University,Nantong 226361,Jiangsu Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2025年第2期211-229,共19页世界胃肠肿瘤学杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.81602792 and No.12205215;and Science and Technology Program of Nantong,No.JC12022103.

摘　　要：BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-6

关 键 词：Esophageal squamous cell carcinoma ADIPOCYTE EXOSOMES MicroRNA RADIOTHERAPY 

分 类 号：R735.1[医药卫生—肿瘤]