High-fidelity of non-small cell lung cancer xenograft models derived from bronchoscopy-guided biopsies

At present, there are two main types of lung cancer xenograft models: those derived from stable cell lines, and patient-derived xenograft models established by surgically resected tissues. However, these animal models may not reflect the biological and genetic characteristics of advanced non-small cell lung cancer (NSCLC). We utilized bronchoscopy-guided biopsy tissues of NSCLC patients to establish xenograft models and analyzed their histopathologic and genotypic fidelity with parental tumors.

Tumor tissues of NSCLC patients taken via bronchoscope were subcutaneously implanted into mice with non-obese diabetic-severe combined immunodeficiency disease for model establishment and serial passage. The histopathology and genotype of the samples from bronchoscopy-guided biopsy-derived xenograft (BDX) models and their parental tumors were detected.

Thirty BDXs out of 114 NSCLC patients (26.32%) were successfully established. Smoking status significantly affected the success rate of NSCLC BDX establishment (P = 0.010). The BDX establishment success rate in squamous cell cancer was higher than in adenocarcinoma, with no significant difference (32.00% vs. 16.21%, P = 0.112). However, the growth rate of passage 1 BDX was slower than that of passages 2 and 3. Almost all NSCLC BDXs maintained similarity to their parental tumor tissues in regard to histologic characteristics, pathological markers, and driver-gene mutations. Only one BDX model lost the epidermal growth factor receptor mutation contained in tumor parental tissue, as a result of heterogeneity.

NSCLC BDXs maintained high fidelity of histopathology and genotype with their original tumors. NSCLC BDXs that possess the actual status of advanced lung carcinoma should be used in preclinical research.