Hsieh Min-Shiau, Lin Meng-Xian, Ho Bing-Ying, Hsiao Jong-Kai
Division of Thoracic Surgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, 23142, Taiwan.
School of Medicine, Tzu Chi University, Hualien, 97004, Taiwan.
Sci Rep. 2025 Jul 2;15(1):23472. doi: 10.1038/s41598-025-05157-z.
We employed PDX models in athymic nude mice to generate lung cancer tumors, aiming to improve early detection and enable personalized treatments. The athymic nude mouse was utilized as the lung cancer PDX model, maintaining the histological and pathological integrity of lung cancer. This model allowed for the analysis of microenvironments through whole transcriptome sequencing to assess gene expression variations across different passages of the PDX model. Candidate genes identified from the RNA-seq analysis were subsequently verified using RT-qPCR. We identified significant changes in genes related to tumor adaptation and immune interactions. Notably, there was a decrease in the expression of Eat-2, Itgb2, Klrd1, and Nkg2d, which are important for NK cell cytotoxic activity. This decrease correlated with the reduction in tumor growth rate from P0 (248 days) to P3 (69 days) to achieve the same tumor volume. Additionally, a decline in the lncRNAs NEAT1 and MALAT1 from PDX passage P0 to P3 was observed and impacting NK cell function and suggesting significant immune system involvement in tumor growth and engraftment. Our findings demonstrate the value of the PDX athymic mice model in lung cancer research. These models are essential for exploring tumor-immune dynamics and developing tailored therapeutic approaches, providing significant insights into tumor behavior and treatment responses.
我们在无胸腺裸鼠中使用人源肿瘤异种移植（PDX）模型来生成肺癌肿瘤，旨在改善早期检测并实现个性化治疗。无胸腺裸鼠被用作肺癌PDX模型，保持肺癌的组织学和病理学完整性。该模型允许通过全转录组测序分析微环境，以评估PDX模型不同传代过程中的基因表达变化。随后使用逆转录定量聚合酶链反应（RT-qPCR）验证从RNA测序分析中鉴定出的候选基因。我们发现与肿瘤适应和免疫相互作用相关的基因有显著变化。值得注意的是，对自然杀伤（NK）细胞细胞毒性活性很重要的Eat-2、整合素β2（Itgb2）、杀伤细胞凝集素样受体亚家族D成员1（Klrd1）和自然杀伤细胞2D（Nkg2d）的表达有所下降。这种下降与肿瘤生长速率从传代0（P0，248天）到传代3（P3，69天）以达到相同肿瘤体积的降低相关。此外，观察到从PDX传代P0到P3长链非编码RNA（lncRNA）NEAT1和转移相关肺腺癌转录本1（MALAT1）的下降，影响NK细胞功能，并表明免疫系统在肿瘤生长和植入中起重要作用。我们的研究结果证明了PDX无胸腺小鼠模型在肺癌研究中的价值。这些模型对于探索肿瘤-免疫动力学和开发定制治疗方法至关重要，为肿瘤行为和治疗反应提供了重要见解。
