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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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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.

2024-09-12 | GSE276387 | GEO

Modeling Tumor Development and Metastasis using Paired Organoids Derived from Patients with Colorectal Cancer Liver Metastases

Project description:Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer patients (CRC). Despite the fact that paired organoids exhibit comparable gene expression and cell morphology. organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC. including SOX2, altered during the progression of CRC. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived organoids to model cancer metastasis. Our data propose that SOX2 is not only a critical biomarker for the development and metastasis of CRC, but also a potent target for the disease treatment.

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Gene expression profiling analysis of RNA-seq data for colorectal cancer organoids and spontaneous metastases mouse models

Project description:We performed RNA-sequencing to investigate the gene expression profiles of colorectal cancer patient-derived organoids (PDO) and PDO-initiated spontaenous metastases mouse models

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Establishment and disease modeling of non-small cell lung cancer organoids

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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Project description:Modeling PD in midbrain-like organoids

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Modeling Tumor Development and Metastasis using Paired Organoids Derived from Patients with Colorectal Cancer Liver Metastases

Project description:Modeling Tumor Development and Metastasis using Paired Organoids Derived from Patients with Colorectal Cancer Liver Metastases

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Patient-derived organoids after neoadjuvant FOLFIRINOX predict therapy resistance in pancreatic ductal adenocarcinoma

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Transcriptomic profiling of patient-derived endometrial cancer organoids (Berg HF)

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