食管鳞癌患者来源移植瘤模型：B-NDG®小鼠与BALB/c裸鼠的比较

目的 探讨不同品系的小鼠对于食管鳞癌患者来源的异种移植瘤（ESCC PDX）成瘤率的影响，为ESCC的临床个体化治疗建立更优势的临床前动物模型。方法 收集22例ESCC患者手术切除的肿瘤组织，分别利用B-NDG®（NSG）鼠和BALB/c裸鼠来建立ESCC PDX模型。通过观察移植瘤成瘤情况，测量移植瘤体积，绘制生长曲线图，计算成瘤率和成瘤时间，HE染色、免疫组化及基因组测序等实验，比较移植瘤组织与原患者肿瘤组织的一致性。结果 22例标本的PDX模型移植结束，发现NSG小鼠ESCC肿瘤发生率（50%，11/22）高于BALB/c裸鼠（18.18%，4/22）（P=0.027）。NSG小鼠的平均肿瘤成瘤时间为75.95 d短于BALB/c小鼠的91.67 d，差异具有统计学意义（P<0.001）。在NSG小鼠和BALB/c小鼠异种移植模型中，肿瘤均能保持病人ESCC肿瘤组织的形态学特征。基因分析结果显示，与BALB/c裸鼠相比，NSG小鼠肿瘤与亲代患者肿瘤样本间的基因相似度更高（P<0.0001）。结论 成功构建了NSG小鼠和BALB/c裸鼠ESCC皮下移植瘤模型，并发现NSG小鼠对于模型成功的建立更具有优势。

Comparison of B-NDG® and BALB/c mouse models bearing patient-derived xenografts ofesophageal squamous cell carcinoma

Objective To investigate the difference of tumor formation in different mouse strains bearing patient-derivedxenograft of esophageal squamous cell carcinoma(ESCC) and establish a better animal model for preclinical study ofindividualized treatment of ESCC. Methods The tumor tissues collected from 22 ESCC patients were used to establishtumor-bearing mouse models in B-NDG® (NSG) mice and BALB/c nude mice. The tumor formation rate and tumor formationtime were compared between the two mouse models, and HE staining, immunohistochemistry and genome sequencing werecarried out to assess the consistency between transplanted tumor tissues in the models and patient-derived tumor tissues.Results The tumor-bearing models were established successfully in both NSG mice (50% , 11/22) and BALB/c nude mice(18.18%, 4/22). The average tumor formation time was significantly shorter in NSG mice than in BALB/c nude mice (75.95 vs91.67 days, P<0.001). In both of the mouse models, the transplanted tumors maintained morphological characteristics identicalto those of patient-derived ESCC tumors. Genetic analysis showed that the xenografts in NSG mice had a greater geneticsimilarity to the patients’ tumors than those in BALB/c nude mice (P<0.0001). Conclusion Mouse models bearing xenografts ofpatient-derived ESCC can be successfully established in both NSG mice and BALB/c nude mice, but the models in the formermouse strain can be more reliable.