Genomic characteristics and drug screening among organoids derived from non‐small cell lung cancer patients

作者：Jing‐Hua Chen, Xiangpeng Chu, Jia‐Tao Zhang, Qiang Nie, Wen‐Fang Tang, Jian Su, Hong‐Hong Yan, Hongping Zheng, Ze‐Xin Chen, Xin Chen, Mengmeng Song, Xin Yi, Pan‐Song Li, Yan‐Fang Guan, Gang Li, Chu‐Xia Deng, Rafael Rosell, Yi‐Long Wu, Wen‐Zhao Zhong · 发表于：Thoracic Cancer · 年份：2020 · DOI：10.1111/1759-7714.13542 · 被引用次数：75 · 研究领域：Cancer Cells and Metastasis、Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics

BACKGROUND: Patient-derived organoid (PDO) models are highly valuable and have potentially widespread clinical applications. However, limited information is available regarding organoid models of non-small cell lung cancer (NSCLC). This study aimed to characterize the consistency between primary tumors in NSCLC and PDOs and to explore the applications of PDOs as preclinical models to understand and predict treatment response during lung cancer. METHODS: Fresh tumor samples were harvested for organoid culture. Primary tumor samples and PDOs were analyzed via whole-exome sequencing. Paired samples were subjected to immunohistochemical analysis. There were 26 antineoplastic drugs tested in the PDOs. Cell viability was assessed using the Cell Titer Glo assay 7-10 days after drug treatment. A heatmap of log-transformed values of the half-maximal inhibitory concentrations was generated on the basis of drug responses of PDOs through nonlinear regression (curve fit). A total of 12 patients (stages I-III) were enrolled, and 7 paired surgical tumors and PDOs were analyzed. RESULTS: PDOs retained the histological and genetic characteristics of the primary tumors. The concordance between tumors and PDOs in mutations in the top 20 NSCLC-related genes was >80% in five patients. Sample purity was significantly and positively associated with variant allele frequency (Pearson r = 0.82, P = 0.0005) and chromosome stability. The in vitro response to drug screening with PDOs revealed high correl...