Establishment and characterization of prostate cancer organoids [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE113741 | GEO | 2018/05/10
REPOSITORIES: GEO
Similar Datasets
Project description:Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis.
2018-05-10 | GSE113709 | GEO
Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.
2015-06-30 | E-GEOD-70380 | biostudies-arrayexpress
Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression.
2015-06-30 | GSE70380 | GEO
Project description:Osteosarcoma (OS) and Ewing’s sarcoma (EW) are the two most common pediatric solid tumors, after brain tumors. Multimodal treatments have significantly improved prognosis in localized disease but outcome is still poor in metastatic patients, for whom therapeutic options are often inadequate. Preclinical drug testing to identify promising treatment options that match the molecular make-up of these tumors is hampered by the lack of appropriate and molecularly well-characterized patient-derived models. To address this need, a panel of patient-derived xenografts (PDX) was established by subcutaneous implantation of fresh, surgically resected OS and EW tumors in NSG mice. Tumors were re-transplanted to next mice generations and fragments were collected for histopathological and molecular characterization. A model was considered established after observing stable histological and molecular features for at least three passages. To evaluate the similarity of the model with primary tumor, we performed a global gene expression profiling and tissue microarrays (TMA), to assess tumor specific biomarkers on tissues from OS/EW tumors and their PDXs (1st and 3rd passage). Moreover, we verified the feasibility of these models for preclinical drug testing. We implanted 61 OS and 29 EW samples: 14/38 (37%) primary OS and 9/23 (39%) OS lung metastases successfully engrafted; while among EW, 5/26 (19%) primary samples and 1/3 (33%) metastases were established. Comparison between patient samples and PDXs, highlighted that histology and genetic characteristics of PDXs were stable and maintained over passages. In particular, correlative analysis between OS and EW samples and their PDXs was extremely high (Pearson’s r range r=0.94-0.96), while patient-derived primary cultures displayed reduced correlation with human samples (r=0.90-0.93), indicating that in vitro adaptation superimpose molecular alterations that create genetic diversion from original tumors. No significant differentially expressed gene profile was observed from the comparison between EW samples and PDXs (fold change > 2, adjusted p <0.05 at paired t-test). In OS, the comparison between OS patient-derived tumors and PDX indicated differences in 397 genes, mostly belonging to immune system functional category. This is in line with the idea that human immune cells are gradually replaced by murine counterparts upon engraftment in the mouse. As proof-of concept, two EW PDX and one OS PDX have been treated with conventional and innovated drugs to test their value in terms of drug-sensitivity prediction. Overall, our study indicated that PDX models maintained the histological and genetic markers of the tumor samples and represent reliable models to test sensitivity to novel drug associations.
2019-08-27 | E-MTAB-7568 | biostudies-arrayexpress
Project description:Informed consent was obtained to collect human mCRPC tissues and generate the patient-derived xenograft tumors as described previously (Labrecque et al., 2019; Nguyen et al., 2017). The study was approved by the University of Washington Human Subjects Division institutional review board (no. 39053). All animal studies were approved by University of Washington IACUC and performed according to NIH guidelines. Molecular characterization of AR+ mCRPC LuCaP PDXs 70CR, 78CR, 81CR, 96CR, 105CR, 136CR and 147CR was previously described (Labrecque et al., 2019; Nguyen et al., 2017). LuCaP PDX 167CR was established from a liver metastasis of 77-year-old Caucasian male who died of abiraterone-, carboplatin- and docetaxel-resistant CRPC. LuCaP 167CR expresses AR, responds to castration and is negative for synaptophysin. PDX cellular morphology recapitulates the original liver metastasis (Supplementary Figure S8A).
2022-04-06 | GSE163220 | GEO
Project description:<p>Using 20 models from the LuCaP mCRPC PDX cohort, including adenocarcinoma and neuroendocrine lineages, the purpose of this study was the systematic testing of > 20 modifications to prostate organoid conditions. 4 of the organoid cell lines were comprehensively evaluated for genomic and phenotypic stability and continued reliance on the AR signaling pathway.</p>
| phs001587 | dbGaP
Project description:Metastatic castrate-resistant prostate cancer (mCRPC) is a genetically and phenotypically heterogeneous cancer where advancements are needed in biomarker discovery and targeted therapy. A critical and often effective component of treatment includes taxanes. We performed one of the first high throughput screens across a cohort of 30 diverse patient-derived CRPC organoids to a library of 78 drugs. Combining quantitative response measures with transcriptomic analyses demonstrated that HNF1 Homeobox A (HNF1A) drives a transcriptional program of taxane resistance, dependent upon cellular inhibitor of apoptosis protein 2 (cIAP2). Monotherapy with cIAP2 inhibitor LCL161 was sufficient to treat HNF1A+ models of mCRPC previously resistant to docetaxel.
2024-04-01 | GSE252216 | GEO
Project description:Metastatic castrate-resistant prostate cancer (mCRPC) is a genetically and phenotypically heterogeneous cancer where advancements are needed in biomarker discovery and targeted therapy. A critical and often effective component of treatment includes taxanes. We performed one of the first high throughput screens across a cohort of 30 diverse patient-derived CRPC organoids to a library of 78 drugs. Combining quantitative response measures with transcriptomic analyses demonstrated that HNF1 Homeobox A (HNF1A) drives a transcriptional program of taxane resistance, dependent upon cellular inhibitor of apoptosis protein 2 (cIAP2). Monotherapy with cIAP2 inhibitor LCL161 was sufficient to treat HNF1A+ models of mCRPC previously resistant to docetaxel.
2024-04-01 | GSE252203 | GEO
Project description:Resistance to androgen deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform to emergent aggressive variant prostate cancer (AVPC) which has neuroendocrine (NE)-like features. To this end, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflects and retains key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. When we compared 15 NE versus 33 AdCa PDX samples, we identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of protein and RNA concordance from these tumors revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa.
Keywords: Proteomics, phosphoproteomics, Neuroendocrine, Adenocarcinoma, biomarkers, surfaceome, secretome, blood proteins, prostate cancer, patient-derived xenograft
2023-06-09 | MSV000092139 | MassIVE