患者来源肾盂癌类器官模型的构建及其在化疗药敏反应中的应用

Patient-derived renal pelvic carcinoma organoids: establishment and sensitivity to chemotherapeutic drugs

摘要:

肾盂癌是一种较为常见的上尿路上皮癌，由于缺乏理想的体外模型，严重阻碍了该类疾病治疗策略研究的进展。本研究基于肾盂癌患者来源肿瘤组织样本，建立肾盂癌类器官培养方法，并基于肾盂癌类器官构建肿瘤化疗药物反应模型。通过免疫组化和荧光实验证实，培养获得的肾盂癌类器官核异型性明显，与亲本肾盂癌组织一致；肾盂癌类器官中肿瘤标志分子CD44和细胞增殖标志分子Ki67均呈强阳性，表明类器官富集肿瘤干细胞，具有较强增殖能力。药物反应实验显示肾盂癌类器官对吡柔比星高度敏感，杀伤作用明显。本研究成功建立了肾盂癌类器官体外培养体系，并进行了初步体外药敏试验，为以肾盂癌为代表的上尿路上皮癌的个体化诊疗提供了新的体外实验模型。

关键词:肾盂癌;类器官;肿瘤干细胞;药物测试

Abstract:

Renal pelvic carcinoma is a common upper urothelial cancer. The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease. This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs. The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism, which was consistent with the tissue samples from renal pelvic carcinoma patients. The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids, indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability. The renal pelvic carcinoma organoids were highly sensitive to pirarubicin, which had obvious killing effects. In brief, this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs. The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.

Key words:renal pelvic carcinoma;organoids;tumor stem cells;drug test