Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30308391_1.fastq.gz | Fastqsanger.gz | |||
| SRR30308391_2.fastq.gz | Fastqsanger.gz | |||
| SRR30308392_1.fastq.gz | Fastqsanger.gz | |||
| SRR30308392_2.fastq.gz | Fastqsanger.gz | |||
| SRR30308393_1.fastq.gz | Fastqsanger.gz |
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Project description:We report a high degree of correlation between PDAC patient derived orgnanoid (PDO) drug sensitivity and clinical responses. This finding supports the utility of PDOs to tailor therapy for individual patients to improve clinical outcomes.
2021-11-10 | GSE187619 | GEO
Project description:Two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the “Classical” and “Basal-like” subtypes. However, the “molecular” classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction. We constructed a PDO library for morphologic and RNA-seq analyses and drug response assays in vitro. PDOs of PDAC were established at a high efficiency (> 70%) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) or densely proliferating inside (DP type). RNA-seq analysis revealed that the “morphological” subtype (GL vs. DP) roughly corresponded to the “molecular” subtype (“Classical” vs. “Basal-like”). The proposed “morphological” classification predicted clinical treatment response and prognosis; the median overall survival of patients with GL type were significantly longer than that of those with DP type (P < 0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK and autophagy inhibition. PDAC PDOs facilitated subtype determination and clinical outcome prediction, thereby advancing precision medicine for PDAC.
2024-04-11 | GSE228801 | GEO
Project description:The IKK kinase was previously found to activate multiple oncogenic and therapy-resistance pathways, including ATM/DDR, BRD4, and JAK/STAT3, independently of canonical NF-B signaling. Here, we show that suppression of IKK, either genetically or pharmacologically, imposes a pro-metastatic activity on colorectal cancer (CRC) patient-derived organoid (PDO) cells, which is linked to an increase in the protein levels of the tight junction protein ZO-1 and CLDN2, and a shift in their migratory mode towards collective migration. Analysis of single-cell (sc)RNA-seq data revealed an accumulation of the tight junction signature in the metastatic populations. Specifically, PDO cells contain three distinct epithelial cell clusters (C2, C4 and C8) with concomitant enrichment of the tight junction and metastasis-associated EpiHR signatures, whose unique genetic signatures are upregulated upon depletion of IKK and enriched in PDO-derived metastases. CLDN2 inhibition or depletion abolishes the metastatic activity of IKK KO PDO cells in vivo. By analyzing human paraffin-embedded CRC specimens, we have detected the presence of vascular tumor infiltrates with cluster-like or glandular phenotypes and high levels of ZO-1 and CLDN2-positive junctions. Collectively, our results suggest that high levels of tight junction proteins in CRC cells impose a pro-metastatic collective CRC cell migration, which can be detected in the vascular infiltrates at diagnosis. We propose that after validation, this type of exploration could be standardized in clinical routine and CLDN2 and the elements defining tight junction-enriched tumor clusters could be considered as metastasis biomarkers and candidate therapeutic target for CRC.
2025-12-01 | PXD057102 | Pride
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
2022-12-01 | GSE213896 | GEO
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived tumor xenografts (PDTXs) have been increasingly used as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. Extensive multiomics characterization of these PDTXs have demonstrated their utility as a suitable model for preclinical studies, representing the diversity of the primary cancers. We performed a multi-factorial integrative analysis of genome-wide ChIP-seq on multiple histone modifications, as well as RNA-seq on subcutaneous PDTXs from 24 PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). In the dataset, ChIP-seq for five distinct histone marks (H3K4me1, H3K27ac, H3K4me3, H3K27me3, and H3K9me3) and RNA-seq was carried out to generate new knowledge on the epigenetic landscapes underlying the heterogeneity of PDAC tissues grown in this manner.
2018-05-29 | E-MTAB-5632 | biostudies-arrayexpress
Project description:Natural killer (NK) cells represent a promising strategy for cellular cancer immunotherapy, but it remains unclear which patients benefit by such therapies. Using co-cultures of primary human allogenic NK cells and patient-derived colon cancer organoids (PDOs), we could stratify PDOs into NK cell “highly susceptible” and “rather resistant” groups reflected by differential expression of NKG2D-ligands, MHC class I and CEACAM. RNA-seq unveiled that hypoxia- and TGF-β-related gene signatures were induced in NK cells after PDO co-culture. Deletion of hypoxia inducible factor (HIF)-2a in primary NK cells or blocking of TGF-β-R1 empowered NK cell-mediated PDO killing. We further demonstrate that upon PDO killing, NK cells adopted an activation/inflammationhigh, cytotoxicitylow, tissue-residencyhigh program as evidenced by CXCR6 and CD49a expression coinciding with a “hot” cytokine/chemokine-rich microenvironment. Since PDO-exposed NK cells largely resemble features of NK cells from CRC patient tissues, our NK cell/PDO platform could be highly relevant for the optimization of NK cell products for personalized medicine.
2025-12-17 | GSE292020 | GEO
Project description:Purpose: Identifying therapeutic targets for Signet Ring Cell Carcinoma (SRCC) of the colon and rectum is a clinical challenge due to the lack of Patient-Derived Organoids (PDO) or Xenografts (PDX). We present a robust method to establish PDO and PDX models to address this unmet need. We demonstrate that these models identify novel therapeutic strategies targeting therapy resistance and peritoneal metastasis. Experimental Design: We derived nine PDO and PDX models from colorectal SRCC patients. Detailed histopathological characterization confirmed the fidelity of these models to the original tumors. Drug sensitivity assays were conducted in vitro and in vivo to assess therapeutic efficacy and impact on peritoneal metastasis. An RNA-seq analysis was performed to identify critical pathways contributing to therapy resistance and metastatic progression. Results: We successfully developed and characterized PDO and PDX models from nine SRCC patients. The SRCC PDO and PDX models exhibited histopathological features consistent with the original tumors, including high mucin content and eccentric nuclei. They demonstrated increased sensitivity to FOLFIRI combined with paclitaxel or vincristine, reducing peritoneal metastasis. RNA-seq analysis revealed the upregulation of autophagy genes in SRCC. Treatment with chloroquine alone resulted in decreased tumor growth and peritoneal metastasis. Conclusions: Our study establishes PDO and PDX models as robust platforms for studying SRCC and identifying potential therapeutic strategies. Combining FOLFIRI with paclitaxel/ vincristine or chloroquine alone inhibits tumor growth and prevents peritoneal metastasis, showing promise for clinical translation. These findings suggest that combining FOLFIRI with IP paclitaxel warrants further investigation in Phase I clinical trials for SRCC patients. These model systems offer a valuable tool to uncover new treatments for these aggressive and therapy-resistant tumors.
2025-01-22 | GSE279979 | GEO