Genomic characteristics and drug screening among organoids derived fromnon-small celllung cancer patients
Por:
Chen, JH, Chu, XP, Zhang, JT, Nie, Q, Tang, WF, Su, J, Yan, HH, Zheng, HP, Chen, ZX, Chen, X, Song, MM, Yi, X, Li, PS, Guan, YF, Li, G, Deng, CX, Rosell, R, Wu, YL and Zhong, WZ
Publicada:
1 ago 2020
Ahead of Print:
1 jul 2020
Resumen:
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 (Pearsonr= 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.
Filiaciones:
Chen, JH:
Southern Med Univ, Sch Clin Med 2, Guangzhou 510515, Guangdong, Peoples R China
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Guangzhou Twelfth Peoples Hosp, Guangzhou, Guangdong, Peoples R China
Chu, XP:
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Zhang, JT:
Southern Med Univ, Sch Clin Med 2, Guangzhou 510515, Guangdong, Peoples R China
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Nie, Q:
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Tang, WF:
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Shantou Univ, Med Coll, Shantou, Peoples R China
Su, J:
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Yan, HH:
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Zheng, HP:
Accurate Int Biotechnol Co, Guangzhou, Guangdong, Peoples R China
Chen, ZX:
Accurate Int Biotechnol Co, Guangzhou, Guangdong, Peoples R China
Chen, X:
Accurate Int Biotechnol Co, Guangzhou, Guangdong, Peoples R China
Song, MM:
Geneplus Beijing Inst, Beijing, Peoples R China
Yi, X:
Geneplus Beijing Inst, Beijing, Peoples R China
Li, PS:
Geneplus Beijing Inst, Beijing, Peoples R China
Guan, YF:
Geneplus Beijing Inst, Beijing, Peoples R China
Li, G:
Southern Med Univ, Sch Clin Med 2, Guangzhou 510515, Guangdong, Peoples R China
Deng, CX:
Univ Macau, Fac Hlth Sci, Canc Ctr, Macau, Peoples R China
:
Inst Invest Ciencies Salut Germans Trias & Pujol, Campus Can Ruti Edifici Muntanya,Ctra Can Ruti, Barcelona, Spain
Wu, YL:
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Zhong, WZ:
Southern Med Univ, Sch Clin Med 2, Guangzhou 510515, Guangdong, Peoples R China
South China Univ Technol, Guangdong Lung Canc Inst, Guangdong Prov Peoples Hosp, Guangdong Key Lab Lung Canc Translat Med, Guangzhou 510080, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou 510080, Guangdong, Peoples R China
Green Published, gold
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