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Genomic characteristics and drug screening among organoids derived from non-small cell lung cancer patients
Chen,Jing Hua1,2,3; Chu,Xiang Peng2; Zhang,Jia Tao1,2; Nie,Qiang2; Tang,Wen Fang2,4; Su,Jian2; Yan,Hong Hong2; Zheng,Hong Ping5; Chen,Ze Xin5; Chen,Xin5; Song,Meng Meng6; Yi,Xin6; Li,Pan Song6; Guan,Yan Fang6; Li,Gang1; Deng,Chu Xia7; Rosell,Rafael8; Wu,Yi Long2; Zhong,Wen Zhao1,2
2020-08-01
Source PublicationThoracic Cancer
ISSN1759-7706
Volume11Issue:8Pages:2279-2290
AbstractBackground: 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 correlation with the mutation profiles in the primary tumors. Conclusions: PDOs are highly credible models for detecting NSCLC and for prospective prediction of the treatment response for personalized precision medicine. Key points: Lung cancer organoid models could save precious time of drug testing on patients, and accurately select anticancer drugs according to the drug sensitivity results, so as to provide a powerful supplement and verification for the gene sequencing.
KeywordConsistency analysis drug screening non-small cell lung cancer patient-derived organoid whole exome sequencing
DOI10.1111/1759-7714.13542
URLView the original
Language英语
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.The Second School of Clinical Medicine,Southern Medical University,Guangzhou,China
2.Guangdong Lung Cancer Institute,Guangdong Provincial People's Hospital,Guangdong Key Laboratory of Lung Cancer Translational Medicine,South China University of Technology & Guangdong Academy of Medical Sciences,Guangzhou,China
3.Guangzhou Twelfth People's Hospital,Guangzhou,China
4.Shantou University Medical College,Shantou,China
5.Accurate International Biotechnology Co.,Guangzhou,China
6.Geneplus-Beijing Institute,Beijing,China
7.University of Macau. Cancer Centre,Faculty of Health Sciences,University of Macau,Macau,China
8.Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol Campus Can Ruti (Edifici Muntanya),Ctra. de Can Ruti,Barcelona,Spain
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GB/T 7714
Chen,Jing Hua,Chu,Xiang Peng,Zhang,Jia Tao,et al. Genomic characteristics and drug screening among organoids derived from non-small cell lung cancer patients[J]. Thoracic Cancer,2020,11(8):2279-2290.
APA Chen,Jing Hua,Chu,Xiang Peng,Zhang,Jia Tao,Nie,Qiang,Tang,Wen Fang,Su,Jian,Yan,Hong Hong,Zheng,Hong Ping,Chen,Ze Xin,Chen,Xin,Song,Meng Meng,Yi,Xin,Li,Pan Song,Guan,Yan Fang,Li,Gang,Deng,Chu Xia,Rosell,Rafael,Wu,Yi Long,&Zhong,Wen Zhao.(2020).Genomic characteristics and drug screening among organoids derived from non-small cell lung cancer patients.Thoracic Cancer,11(8),2279-2290.
MLA Chen,Jing Hua,et al."Genomic characteristics and drug screening among organoids derived from non-small cell lung cancer patients".Thoracic Cancer 11.8(2020):2279-2290.
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