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Modeling Lung Adenocarcinoma Metastases Using Patient-Derived Organoids

ABSTRACT: Modeling Lung Adenocarcinoma Metastases Using Patient-Derived Organoids

PROVIDER: PRJNA1157185 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30552073_1.fastq.gz	Fastqsanger.gz
	SRR30552073_2.fastq.gz	Fastqsanger.gz
	SRR30552074_1.fastq.gz	Fastqsanger.gz
	SRR30552074_2.fastq.gz	Fastqsanger.gz
	SRR30552075_1.fastq.gz	Fastqsanger.gz

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Modeling Lung Adenocarcinoma Metastases Using Patient-Derived Organoids

Project description:Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized patient-derived organoids (PDOs) from patients with lung adenocarcinoma (LUAD), we establish an in vivo metastasis model that preserves the biologic features of human LUAD metastases. Results of whole-genome and RNA sequencing performed in this study establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRASG12C PDOs to Sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD.

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Project description:Purpose: The goal of this study is to establish and molecularly characterize non-small cell lung cancer (NSCLC) organoids. Generation of NSCLC organoids would provide additional preclinical models for drug screening and biomarker discovery. Methods: Patient lung tumors and previously established patient-derived xenografts (PDX) were processed to generate organoids. Total RNA was extracted and subjected to RNA-seq to examine the gene expression similarity between patient/PDX/organoid of the same model using t-SNE clustering. Results: Through RNA-sequencing, we generated TPM values of patient, PDX and organoid samples of 5 models. t-SNE analysis showed that the patient/PDX/organoid of the same models clustered together. The lung adenocarcinoma samples formed a separate cluster from the squamous cell carcinoma samples based on gene expression. Conclusions: Our study introduces the establishment of NSCLC organoids and demonstrates the gene expession similarity of the organoid model to its corresponding PDX and patient sample.

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