上海口腔医学 ›› 2025, Vol. 34 ›› Issue (1): 25-31.doi: 10.19439/j.sjos.2025.01.005

• 论著 • 上一篇    下一篇

患者来源的唾液腺恶性肿瘤类器官放疗模型的构建与应用评价

徐凤1,2, 孟箭1,2,3, 陈霖2,3, 陈寅瑜2,3, 王守鹏2   

  1. 1.徐州医科大学 徐州临床学院, 江苏 徐州 221000;
    2.徐州市中心医院 口腔科, 江苏 徐州 221000;
    3.徐州医科大学 口腔医学院, 江苏 徐州 221000
  • 收稿日期:2023-12-15 修回日期:2024-02-06 发布日期:2025-03-05
  • 通讯作者: 孟箭,E-mail: mrocket@126.com
  • 作者简介:徐凤(1998-),女,硕士,住院医师,E-mail: 931530231@qq.com
  • 基金资助:
    国家口腔疾病临床医学研究中心开放课题(NCRCO-202101);江苏省老年健康科研项目(LKM2024031);徐州市重点研发计划(KC21187);徐州医科大学附属医院发展基金项目(XYFY202207)

Construction and application of organoid radiological model of patient-derived salivary gland malignant tumors

XU Feng1,2, MENG Jian1,2,3, CHEN Lin2,3, CHEN Yin-yu2,3, WANG Shou-peng2   

  1. 1. Xuzhou Clinical College of Xuzhou Medical University. Xuzhou 221000;
    2. Department of Stomatology, Xuzhou Central Hospital. Xuzhou 221000;
    3. Affiliated Stomatological Hospital of Xuzhou Medical University. Xuzhou 221000, Jiangsu Province, China
  • Received:2023-12-15 Revised:2024-02-06 Published:2025-03-05

摘要: 目的: 构建患者来源的唾液腺恶性肿瘤类器官近距离放疗模型,评价125I粒子干预对不同类器官活性的影响,探讨该模型指导唾液腺恶性肿瘤患者临床个性化治疗的可行性。方法: 选取徐州市中心医院收治的唾液腺恶性肿瘤[黏液表皮样癌(mucoepidermoid carcinoma,MEC)、腺样囊性癌(adenoid cystic carcinoma,ACC)和腺泡细胞癌(acinic cell carcinoma,AciCC)]患者活检标本,运用3D培养法构建类器官模型,检测肿瘤组织标本与类器官样本免疫组织化学指标表达水平。构建近距离放疗模型,采用3D细胞微组织检测法检测不同剂量125I粒子对类器官活性的影响,绘制活性曲线并计算IC50值。采用 GraphPad Prism 9.0软件对数据进行统计学分析。结果: H-E染色和免疫组织化学染色结果鉴定类器官与标本肿瘤具有同源性。125I粒子对5例唾液腺恶性肿瘤类器官(1例ACC、2例AciCC和2例MEC)的IC50均值分别为8 508、6 053、5 203、10 379和7 743 cGy;AciCC对125I粒子的敏感性更高,同种肿瘤的不同个体对125I粒子的敏感性存在差异。结论: 针对患者来源的唾液腺恶性肿瘤标本建立体外肿瘤类器官培养平台,检测其组织学结构、分子标志物表达符合原始患者肿瘤细胞的特征。类器官近距离放疗模型干预结果提示,该模型具有明显个体化差异,为125I粒子应用于一些局部、复发、晚期、低分化或手术治疗意义不大的患者的有效性提供了依据。该模型建模时间短、价格低、可高通量检测,可在体外预测患者治疗反应,帮助恶性肿瘤的风险评估和建立个体化精准治疗方案。

关键词: 类器官, 唾液腺恶性肿瘤, 125I粒子, 抗癌活性

Abstract: PURPOSE: To construct a brachytherapentic model of patient-derived salivary gland malignant tumor organoids, and evaluate the impact of 125I radioactive seeds intervention on the activity of different organoids, and explore the feasibility of using this model to guide clinical personalized treatment of salivary gland malignant tumors. METHODS: Biopsy specimens from patients with malignant salivary gland tumors including mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma(ACC) and acinic cell carcinoma (AciCC) from Xuzhou Central Hospital were collected, and 3D culture method was used to construct the organoid model. The expression levels of immunohistochemical indicators in salivary gland malignant tumor tissue samples and organoid samples were detected. Brachytherapentic model was constructed and the effect of different doses of 125I seeds on organoid activity were detected using 3D cell viability assay. The activity curves were plotted and the IC50 values were calculated. The data were analyzed by GraphPad Prism 9.0 software. RESULTS: H-E staining results and immunohistochemical staining results identified homology between organoids and specimen tumors. The mean IC50 values of 125I seeds on 5 cases of salivary gland malignant tumor organoids (1 case of ACC, 2 cases of AciCC and 2 cases of MEC) were 8 508, 6 053, 5 203, 10 379 and 7 743 cGy, respectively. AciCC has a higher sensitivity to 125I seeds, and the sensitivity of 125I seeds varied among individuals of the same type of tumor. CONCLUSIONS: An in vitro tumor organoid culture platform has been established for specimens from patients with salivary gland malignant tumors, and its morphological, histological structure, and molecular marker expression are consistent with the characteristics of tumor cells in the original specimens. Intervention results indicated that the model has significant individualized differences, providing a theoretical basis and methodological reference for the effectiveness of 125I seeds in some patients with local, recurrent, advanced, poorly differentiated, or unresectable tumours. This model has the advantages of low cost, short modeling time, and high throughput detection. It can predict the patient's post-treatment response in vitro, guide risk assessment of malignant tumors in clinical practice, and establish personalized and precise treatment plans.

Key words: Organoid, Salivary gland malignant tumor, 125I radioactive seed, Anticancer activity

中图分类号: