2d224bdb-0368-4471-aef3-1b98856e0c55 - samples
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ABSTRACT:
PROVIDER: EGAD00001005357 | EGA |
REPOSITORIES: EGA
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Project description:In this study, we have generated patient-derived organoids (PDOs) from primary and metastatic lesions of gastrointestinal cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma and evaluated their ability to predict donor tumor drug response. Specifically, we examined individual PDO responses to therapeutic agents with the observed clinical responses of donor patients to the same treatments and demonstrated an approximately 80% concordance rate. Importantly, we found a profound influence of culture media in PDOs phenotypes, we observed a significant difference in response to common PDAC chemotherapies, distinct morphologies, and transcriptomes between media in the same PDOs. These studies demonstrate the important role of culture media when using PDOs to inform patient care and predict response across a spectrum of GI cancers. We compared transcriptome data from pancreatic ductal adenocarcinoma patient-derived organoids in two media (WNT and PaTOM).
2022-10-12 | GSE212014 | GEO
Project description:We have performed gene expression profiling of patient-derived tumor organoids (PDOs) and tissue samples of resected liver metastases from patients with metastatic colorectal cancer.
2026-04-20 | GSE294511 | GEO
Project description:Patient-derived organoids (PDOs) model treatment response of metastatic gastrointestinal cancers.
| PRJNA427119 | ENA
Project description:Colorectal cancer (CRC) is a commonly occurring cancer worldwide. Metastasis and recurrence are the major causes of cancer-related death. CRC progression is a multistep process, and extensive efforts have been made to identify the genomic and transcriptomic alterations that occur during this process. However, whether primary tumors and metastatic lesions possess distinct biological features remains unclear. We established 74 patient-derived organoids (PDOs) from primary tumors and patient-matched metastatic and recurrent lesions.
2021-04-01 | GSE128213 | GEO
Project description:Colorectal cancer (CRC) is one of the most lethal cancers when it progresses to the advanced/metastatic stage. Treatment options for refractory metastatic colorectal cancer (mCRC) are limited. Therefore, there is an urgent need to develop effective treatment methods for metastatic colorectal cancer. In this study, we screened a library of small molecules for inhibitors of CRC recurrence using CRC cell lines and patient-derived organoids (PDOs) from metastatic, heavily pretreated CRC. The in vivo efficacy of LS-1-2 was evaluated in the HCT116 and the resistant HCT8 cell lines, patient-derived xenografts(PDXs) including refractory mCRC, and a liver metastasis mouse model. Biotin pull-down and liquid chromatography tandem-mass spectrometry (LC-MS/MS) were performed to identify proteins that interact with LS-1-2. The genome-wide gene expression and quantitative phosphoproteomic analyses were performed to determine the signaling pathway involved in LS-1-2. Molecular docking, molecular dynamics analysis and cellular thermal shift assays were used to predict and validate the binding sites of LS-1-2 on non-muscle Myosin IIA (NMHC IIA). Our results showed that LS-1-2 exhibited broad antiproliferative effects on a series of CRC cell lines and PDOs. The in vivo anti-tumor efficacy of LS-1-2 was demonstrated across cell line- and patient-derived xenografts and in the liver metastatic CRC model. NMHC IIA was identified as a direct target of LS-1-2, and LS-1-2 competitively inhibited the phosphorylation of NMHC IIA at S1943 and S1714 by CK2. NMHC IIA phosphorylation promoted CRC cell proliferation and invasion, which was reduced by LS-1-2. NMHC IIA phosphorylation-mediated YAP activity induced activation of AKT and inactivation of FOXO3a and was suppressed by LS-1-2. In conclusion, our findings suggest that NMHC IIA phosphorylation can be used as a potential molecular target in CRC metastasis, and that targeting NMHC IIA phosphorylation by LS-1-2 may be a promising strategy for the treatment and prevention of CRC metastasis.
2023-09-02 | PXD044543 | Pride
Project description:We characterized the epigenetic landscape of human colorectal cancer (CRC). To this extent, we performed gene expression profiling using high throughput sequencing (RNA-seq) and genome wide binding/occupancy profiling (ChIP-seq) for histone modifications correlated to transcriptional activity, enhancers, elongation and repression (H3K4me3, H3K4me1, H3K27Ac, H3K36me3, H3K27me3) in patient-derived organoids (PDOs), and in normal and tumoral primary colon tissues. We also generated ChIP-seq data for transcription factors YAP/TAZ in human CRC PDOs.
2021-02-23 | E-MTAB-8416 | biostudies-arrayexpress
Project description:We characterized the epigenetic landscape of human colorectal cancer (CRC). To this extent, we performed gene expression profiling using high throughput sequencing (RNA-seq) and genome wide binding/occupancy profiling (ChIP-seq) for histone modifications correlated to transcriptional activity, enhancers, elongation and repression (H3K4me3, H3K4me1, H3K27Ac, H3K36me3, H3K27me3) in patient-derived organoids (PDOs), and in normal and tumoral primary colon tissues. We also generated ChIP-seq data for transcription factors YAP/TAZ in human CRC PDOs.
2021-03-10 | E-MTAB-8448 | biostudies-arrayexpress
Project description:Background: Patient derived organoids (PDOs) can be established from colorectal cancers as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented through interferon gamma (IFN) or MEK-inhibitors. Methods: Four PDOs from chemotherapy refractory and one from a treatment naïve CRC were expanded to replicates with 100 million cells each, and HLA class I and class II peptide ligands were analysed by MS. Results: We identified an average of 9,936 unique peptides per PDO which compares favourably against published immunopeptidomics studies, suggesting high sensitivity. Loss of heterozygosity of the HLA locus was associated with low peptide diversity in one PDO. Peptides from genes without detectable expression by RNA-sequencing were rarely identified by MS. Only 3 out of 612 non-silent mutations encoded for neoantigens that were detected by MS. Treatment of four PDOs with IFN upregulated HLA class I expression and qualitatively changed the immunopeptidome, with increased presentation of IFN-inducible genes. HLA class II presented peptides increased on average 16-fold with IFN treatment. MEK-inhibitor treatment showed no consistent effect on class I or II HLA expression or the peptidome. Importantly, no additional HLA class I or II presented neoantigens became detectable with any treatment. Conclusions: Only 3 out of 612 non-synonymous mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this.
2019-11-27 | PXD014017 | Pride
Project description:Rectal cancer is most frequently diagnosed at a locally advanced stage and treated by neoadjuvant chemoradiation. Current efforts to improve treatment outcome are focused on intensifying neoadjuvant chemotherapy, which is however associated with higher levels of toxicity. To discover alternative strategies, we established patient-derived rectal cancer organoids (PDOs) that reflect clinical radiosensitivity and used these organoids to screen 1596 drug-radiation combinations. We found that inhibitors of RAS-MAPK signaling, especially MEK inhibitors, strongly enhance radiation response. Mechanistically, MEK inhibitors suppressed radiation-induced activation of RAS-MAPK signaling, and selectively downregulated RAD51, a key component of the homologous recombination DNA repair pathway. Through testing drug-drug-radiation combinations in organoids and cell lines, we identified that a combined PARP and MEK inhibition can further enhance radiosensitivity of colorectal cancers, which was confirmed in mouse xenograft models. Our data support clinical testing of MEK and PARP combination therapy with radiation in locally advanced rectal cancers as an alternative to chemoradiation Microarrays were used to investigate the effect of radiation treatment on gene expression in three patient-derived colorectal cancer organoid lines.
2025-04-23 | GSE294953 | GEO
Project description:Colorectal cancer (CRC) arises in the colorectal tissue driven by genetic disorder or the accumulation of somatic mutations, leading to abnormal epithelial cell growth. In this study, we employed single-nucleus multi-omics analysis, including single-nucleus RNA-seq and single-nucleus ATAC-seq, on over 100,000 high-quality nuclei to investigate the molecular landscape of both primary tissue and patient-derived organoids (PDOs). Our analysis showed that normal PDOs (N-PDOs) derived from tissue adjacent to tumors replicate the cellular composition and differentiation trajectory of colorectal crypts. In contrast, tumor PDOs (T-PDOs) showed patient-specific transcriptomic and epigenomic heterogeneity yet consistently maintained a stem cell-like state. T-PDOs retained the somatic mutation profile of the primary tumor while also exhibiting de novo mutations not detected in either the primary tumor or N-PDOs. Notably, inferred cell-cell interaction analysis highlighted the activin signaling pathway as a potential unique feature of fibroblast-epithelial interactions within tumor microenvironment. This study provides a comprehensive view of the transition from normal to malignant colorectal epithelium and underscores the utility of PDOs as faithful model for capturing both conserved and patient-specific features of colorectal cancer.
2025-07-18 | GSE294559 | GEO