【摘要】 目的 初步探索条件重编程培养体系在膀胱癌精准治疗中的应用。方法 收集2017年3月—2020年12月于复旦大学附属中山医院接受手术的47例膀胱癌患者的肿瘤组织和（或）尿液样本。利用条件重编程培养技术建立可稳定增殖的肿瘤原代细胞系，通过高通量药物测试平台，检测条件重编程细胞（conditional reprogramming cell,CRC）对临床常用化学治疗药物的敏感性，计算半抑制浓度并进行标准化评分（Z-score）。根据评分将患者分为敏感组（Z-score<0）与不敏感组（Z-score>0）。收集患者的临床资料及随访信息，采用Kaplan-Meier法计算患者生存率并绘制生存曲线，组间比较采用log-rank检验。采用Cox比例风险回归分析药物敏感性对患者预后的影响。结果 成功建立50株CRC，其中组织来源27株，尿液来源23株。药物敏感性热图显示，不同患者的CRC对药物的响应性存在显著差异。多因素Cox回归分析显示，敏感组患者的死亡风险呈降低趋势，但差异无统计学意义（风险比为0.38,95%CI为0.05～2.82,P=0.340）。排除用药信息缺失无随访记录的患者后，生存分析显示，敏感组生存时间有长于不敏感组的趋势，两组患者在总生存期和无复发生存期方面的差异均无统计学意义（P值均>0.05）。结论 条件重编程培养体系适用于大规模的药物敏感性测试，且药物敏感性测试结果与患者临床预后存在一定的相关性；基于CRC的药物敏感性测试结果可为个性化治疗方案提供一定的参考价值。更多还原

【Abstract】 Objective To preliminarily investigate the application of the conditional reprogramming culture system in treatment of bladder cancer.Methods Tumor tissues and/or urine samples were collected from 47 bladder cancer patients who underwent surgery at Zhongshan Hospital,Fudan University,between March 2017 and December 2020.Conditionally reprogrammed primary tumor cell lines with stable proliferative capacity were established using conditional reprogramming culture techniques.The drug sensitivity of the conditional reprogramming cells（CRC）to commonly used chemotherapeutic agents was assessed using a high-throughput drug-testing platform.Half-maximal inhibitory concentrations(IC₅₀)were calculated and standardized using Z-score normalization.Patients were stratified into sensitive（Z-score <0）and nonsensitive（Z-score>0）groups.Clinical characteristics and follow-up data were collected.Survival rate was estimated using the Kaplan-Meier method,and survivorship curve was plotted.The log-rank test was used for between-group comparisons.Cox proportional hazards regression analysis was performed to evaluate the impact of drug sensitivity on patient prognosis.Results A total of 50 CRC lines were successfully established,including 27 lines derived from tumor tissues and 23 lines derived from urine samples. Drug sensitivity heatmaps revealed significant heterogeneity in CRC responses to chemotherapeutic agents among patients.Multivariable Cox regression analysis revealed a trend toward reduced mortality risk in the drug-sensitive group.However,there was no significant difference in the mortality risk between sensitive and nonsensitive groups（hazard ratio:0.38,95%CI:0.05 to 2.82,P=0.340）.After excluding patients with incomplete treatment information or missing follow-up data,survival analyses revealed a tendency toward longer survival in the drug-sensitive group compared with the non-sensitive group.However,no statistically significant differences were observed between the two groups in either overall survival or recurrence-free survival（P>0.05）.Conclusion The conditional reprogramming culture system is suitable for large-scale drug sensitivity testing,and the results show a moderate concordance with clinical outcomes.Drug sensitivity data derived from CRC may provide valuable guidance for the development of individualized therapeutic strategies.更多还原