Liao Hong, Zhou Shixin, Chen Si, Li Jun, Zhang Zongqi, Meng Ling, Liu Qiliang, Wu Yuan, He Yuanqiao, Li Ming
Department of Medicine, The Eighth Hospital of Wuhan, Wuhan, Hubei, People's Republic of China.
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Cancer Manag Res. 2023 Feb 17;15:165-174. doi: 10.2147/CMAR.S389339. eCollection 2023.
Non-small-cell lung cancer (NSCLC) comprises approximately 80% of all lung malignancies. The 5-year survival rate of patients with advanced lung cancer who lost their chances of surgery is approximately 15%. Suitable animal models are important in screening individualized treatment plans for patients with lung cancer, evaluating the pre-clinical efficacy of new drugs, and conducting basic research.
In this study, we collected malignant pleural effusion (MPE) samples from 31 patients with NSCLC, successfully constructed 11 NSCLC patient-derived xenografts (PDXs), and analyzed the factors affecting their successful establishment. Primary PDX tumors were characterized using histological analysis, immunohistochemistry, short tandem repeat (STR) profiling, and cytogenetic analysis.
The PDXs preserved the histopathology and protein expression pattern of parental tumors. STR analysis revealed the PDX tissue and a tumor tissue of the same individual origin. Statistical analysis showed that the survival time of patients reflected the malignant degree of MPEs to a certain extent, thus affecting the establishment of PDXs. However, the age, gender, and clinical and biochemical indicators of the patients did not affect the establishment of PDX models.
These data suggest that the established NSCLC PDXs preserved the molecular characteristics of primary lung cancer and can serve as a new tool to elucidate the pathogenesis of tumors, explore new treatment methods, and conduct the research and development of new drugs for tumors.
非小细胞肺癌(NSCLC)约占所有肺恶性肿瘤的80%。失去手术机会的晚期肺癌患者的5年生存率约为15%。合适的动物模型对于筛选肺癌患者的个体化治疗方案、评估新药的临床前疗效以及开展基础研究至关重要。
在本研究中,我们收集了31例NSCLC患者的恶性胸腔积液(MPE)样本,成功构建了11个NSCLC患者来源的异种移植瘤(PDXs),并分析了影响其成功建立的因素。使用组织学分析、免疫组织化学、短串联重复序列(STR)分析和细胞遗传学分析对原发性PDX肿瘤进行表征。
PDXs保留了亲本肿瘤的组织病理学和蛋白质表达模式。STR分析显示PDX组织与同一来源个体的肿瘤组织一致。统计分析表明,患者的生存时间在一定程度上反映了MPE的恶性程度,从而影响PDXs的建立。然而,患者的年龄、性别以及临床和生化指标均不影响PDX模型的建立。
这些数据表明,所建立的NSCLC PDXs保留了原发性肺癌的分子特征,可作为阐明肿瘤发病机制、探索新治疗方法以及开展肿瘤新药研发的新工具。