Establishment and Characterization of Patient-Derived Xenograft Model of Non-Small-Cell Lung Cancer Derived from Malignant Pleural Effusions

Abstract

Hong Liao,1,* Shixin Zhou,2,* Si Chen,3 Jun Li,3 Zongqi Zhang,3 Ling Meng,3 Qiliang Liu,4 Yuan Wu,3 Yuanqiao He,5– 7 Ming Li3 1Department of Medicine, The Eighth Hospital of Wuhan, Wuhan, Hubei, People’s Republic of China; 2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Oncology, Wuhan Pulmonary Hospital, Wuhan, Hubei, People’s Republic of China; 4Department of Pathology, Wuhan Pulmonary Hospital, Wuhan, Hubei, People’s Republic of China; 5Department of Laboratory Animal Science, Nanchang University, Nanchang, People’s Republic of China; 6Jiangxi Province Key Laboratory of Laboratory Animal, Nanchang, People’s Republic of China; 7Nanchang Royo Biotech Co, Ltd, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Li, Department of Oncology, Wuhan Pulmonary Hospital, No. 28 Baofeng Road, Qiaokou District, Wuhan City, Hubei Province, 430030, People’s Republic of China, Tel [phone], Email [email protected] Yuanqiao He, Department of Laboratory Animal Science, Nanchang University, No. 999, Xuefu Road, Nanchang, Jiangxi, 330031, People’s Republic of China, Tel [phone], Email [email protected]: 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.Patients and Methods: 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.Results: 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.Conclusion: 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.Keywords: PDX, translational model, short tandem repeat profiling, cytogenetic analysis, survival time

Keywords

• pdx
• translational model
• short tandem repeat profiling
• cytogenetic