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

机译:源自支气管镜引导活检的非小细胞肺癌异种移植模型的高保真度

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AbstractBackgroundAt 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.MethodsTumor 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.ResultsThirty 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.ConclusionsNSCLC 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.
机译:摘要背景目前,肺癌的异种移植模型主要有两种:从稳定细胞系衍生的模型和通过手术切除的组织建立的患者来源的异种移植模型。但是,这些动物模型可能无法反映晚期非小细胞肺癌(NSCLC)的生物学和遗传特征。我们利用支气管镜引导的非小细胞肺癌患者活检组织建立异种移植模型,并分析其与亲本肿瘤的组织病理学和基因型保真度。建立和连续通过。检测了来自支气管镜引导的活检组织异种移植(BDX)模型及其父母肿瘤的样品的组织病理学和基因型。结果成功建立了114例NSCLC患者中的30例BDX(26.32%)。吸烟状况显着影响非小细胞肺癌BDX建立的成功率(P = 0.010)。鳞状细胞癌中BDX建立成功率高于腺癌,无显着差异(32.00%对16.21%,P = 0.112)。但是,第1代BDX的生长速度比第2代和第3代慢。在组织学特征,病理标记和驱动基因突变方面,几乎所有NSCLC BDX都与其亲本肿瘤组织保持相似。由于异质性,只有一个BDX模型丧失了肿瘤亲本组织中所包含的表皮生长因子受体突变。结论NSCLC BDXs保持了其原始肿瘤的组织病理学和基因型的高保真度。在临床前研究中应使用具有晚期肺癌实际状况的NSCLC BDX。

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