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Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor [RNA-seq]

ABSTRACT: RNA sequencing demonstrates molecular profiles common to primary tumor, PDX and organoid models

ORGANISM(S): Homo sapiens

PROVIDER: GSE114453 | GEO | 2020/06/01

REPOSITORIES: GEO

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Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors.

Project description:Patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid systems show great promise for understanding the biological underpinnings of disease and advancing therapeutic precision medicine. Despite the increased use of organoids, the fidelity of molecular features, genetic heterogeneity, and drug response to the tumor of origin remain important unanswered questions limiting their utility. To address this gap in knowledge, primary tumor- and patient-derived xenograft (PDX)-derived organoids, and 2D cultures for in-depth genomic and histopathologic comparisons with the primary tumor were created. Histopathologic features and PDAC representative protein markers (e.g., claudin 4 and CA19-9) showed strong concordance. DNA- and RNA-sequencing (RNAseq) of single organoids revealed patient-specific genomic and transcriptomic consistency. Single-cell RNAseq demonstrated that organoids are primarily a clonal population. In drug response assays, organoids displayed patient-specific sensitivities. In addition, the in vivo PDX response to FOLFIRINOX and gemcitabine/abraxane treatments were examined, which was recapitulated in vitro with organoids. This study has demonstrated that organoids are potentially invaluable for precision medicine as well as preclinical drug treatment studies because they maintain distinct patient phenotypes and respond differently to drug combinations and dosage. IMPLICATIONS: The patient-specific molecular and histopathologic fidelity of organoids indicate that they can be used to understand the etiology of the patient's tumor and the differential response to therapies and suggests utility for predicting drug responses.

| S-EPMC6647028 | biostudies-literature

Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-01 | GSE114455 | GEO

Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor [Drop-seq]

Project description:In this study, we applied Drop-seq, a high throughput single cell RNA-seq platform, to characterize the different cell types present in pancreatic cancer organoids. We sequenced the transcriptomes of 7675 single cells from organoids derived from a patient undergoing a Whipple procedure for pancreatic ductal adenocarcinoma (PDAC). We then developed a novel clustering approach based on a class of probabilistic generative models called topic models, leading to the identification of subpopulations of cells.

2020-06-01 | GSE114454 | GEO

Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor

Project description:Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor

| PRJNA471419 | ENA

Pancreatic adenocarcinoma human organoids share structural and genetic features with primary tumors

Project description:Pancreatic adenocarcinoma human organoids share structural and genetic features with primary tumors

| PRJNA498740 | ENA

Pancreatic adenocarcinoma human organoids share structural and genetic features with primary tumors

Project description:Pancreatic adenocarcinoma human organoids share structural and genetic features with primary tumors

| PRJNA498741 | ENA

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.

2019-11-26 | GSE119004 | GEO

Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor [RNA-seq]

Project description:Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor [RNA-seq]

| PRJNA471423 | ENA

Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor [Drop-seq]

Project description:Organoids derived from pancreatic adenocarcinoma patients share morphological and genetic features with the primary tumor [Drop-seq]

| PRJNA471422 | ENA

Expression Analysis of Mouse Tumor and Metastatic Pancreatic Ductal Adenocarcinoma Organoids

Project description:This study used Illumina strand-specific, paired-end RNA-sequencing to examine gene expression differences between matched murine tumor- and metastasis-derived mouse pancreatic ductal adenocarcinoma (PDAC) cells grown as three-dimensional, organoid cultures. The study analyzed 16 organoid lines derived from matched primary PDAC tumors and PDAC metastases from 6 KPC (KrasLSL-G12D; Trp53LSL-R172H; Pdx1-Cre) mice.

2020-06-16 | GSE142467 | GEO

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