Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LAKTP_MTO orthotopic primary caecum tumours from Galunisertib-treated C57BL/6J mice

ABSTRACT: Mouse tumour organoids (MTOs) derived from a compound mutant (LAKTP) intestinal cancer model were orthoptopically transplanted into syngeneic C57BL/6J mice. Tumour-bearing mice were treated with TGF-beta inhibitor Galunisertib or vehicle control. Whole tumour mRNA was extracted from primary tumours and expression profiling was performed with the objective to characterize the tumour microenvironment (TME). As a TGF-beta-activated TME has been associated to a poor prognosis and the CRC consensum molecular subtype CMS4, and the mouse model was found to have such an activated TME, we used the array data to classify these tumours in this mouse model system as CMS4-like. Furthermore, treatment with TGF-beta inhibitor reduced the fibroblast- and T cell-specific TGF-beta response signatures, also associated to poor prognosis in human CRC. This treatment was associated to a strong reduction/prevention of liver metastasis, as well as a reduction of primary tumour (and local carcinomatosis) size.

ORGANISM(S): Mus musculus

PROVIDER: GSE103562 | GEO | 2018/02/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression profiles of cell populations purified from human CRC (4 ways)

2013-01-17 | GSE39396 | GEO

Transcriptomics and proteomics reveal distinct biology for lymph node metastases and tumor deposits in colorectal cancer

Project description:Objective: Both lymph node metastases (LNMs) and tumor deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aims to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Design: Spatially resolved transcriptomic analysis using Digital Spatial Profiling was performed on TDs and LNMs from 10 CRC patients using 1,388 RNA targets, for the tumor cells and tumor microenvironment (TME). Shotgun proteomics identified 5,578 proteins in 12 different patients. Differences in RNA and protein expression were analyzed, and spatial deconvolution was performed. Image-based CMS (imCMS) analysis was performed on all TDs and LNMs included in the study. Results: Transcriptome and proteome profiles identified distinct clusters for TDs and LNMs in both the tumor and TME segment, with upregulation of matrix remodeling, cell adhesion/motility and epithelial mesenchymal transition (EMT) in TDs (all p<0.05). Spatial deconvolution showed a significantly increased number of fibroblasts, macrophages, and regulatory T cells (p<0.05) in TDs. In consistency with a higher fibroblast and EMT component, imCMS classified 62% of TDs as poor prognosis subtype CMS4 compared to 36% of LNMs (p<0.05). Conclusion: Compared to LNMs, TDs have a more invasive state; involving a distinct TME and upregulation of EMT, which are reflected in a more frequent histological classification of TDs as CMS4. These results emphasize the heterogeneity of locoregional spread the fact that TDs should merit more attention both in future research and during staging.

2023-09-19 | PXD041625 | Pride

Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumour human scRNA-Seq]

Project description:Metastasized colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Besides hepatic metastasis, peritoneal carcinomatosis is the major cause of death in UICC stage IV CRC patients. Insights into differential site-specific reconstitution of tumour cells and the corresponding tumour microenvironment are still missing. Here, we analysed the transcriptome of single cells derived from murine multivisceral CRC and gave insight into the inter-metastatic cellular heterogeneity regarding tumour epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumour epithelium during peritoneal metastasis as well as an autologous feed-forward loop in cancer stem cells. We furthermore deciphered a metastatic dysfunctional adaptive immunity by a loss of B cell dependent antigen presentation and consecutive effector cell exhaustion. Consequently, we demonstrate the high human-mimicking potential of this murine metastatic CRC model and provide a valid tool for future site-specific preclinical drug testing.

2024-01-10 | GSE234804 | GEO

Expression profiles of cell populations purified from human CRC (3 ways)

2013-01-17 | GSE39395 | GEO

Peritoneal Carcinomatosis of gastric cancer

Project description:Peritoneal carcinomatosis is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. A major mechanism in peritoneal carcinomatosis is the dissemination of cancer cells into the abdominal cavity, mainly in diffuse gastric adenocarcinoma. The features that enable diffuse primary gastric tumours to develop peritoneal dissemination have been little investigated and are only incompletely understood. We therefore compared the gene expression profile in patients with diffuse primary gastric cancer with and without peritoneal carcinomatosis. Specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Keywords: Disease state analysis

2008-01-31 | GSE8657 | GEO

Expression profiles of cell populations purified from human CRC (4 ways)

Project description:The survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease. We purified by FACS CD31(+), CD45(+), FAP(+) and Epcam(+) populations from fresh CRC samples and assessed their gene expression profiles Freshly obtained tumours from 6 CRC patients treated at Hospital del Mar or Hospital Clinic (Barcelona, Spain) were minced and incubated with Collagenase IV (100 U mL-1). Enzymatic reaction was stopped by adding 10% FBS, single cells were collected by sequential filtering and resuspended in ammonium chloride (0.15M) to lyse erythrocytes. Cells were stained with FAP unconjugated rabbit antibody. After two washes with HBSS, cells were stained with an APC conjugated anti-rabbit antibody; anti-hEPCAM/TROP1-FITC, anti-CD31-PE and anti-CD45-PE-Cy7 conjugated antibody. Dead cells were labelled with Propidium Iodide. Fluorescence Activated Cell Sorting (FACS) was used to separate 2000 cells from each population; [CD45(+), EPCAM(-), CD31(-), FAP(-)], [CD45(-) EPCAM(+), CD31(-), FAP(-)], [CD45(-), EPCAM(-), CD31(+),FAP(-)] and [CD45(-), EPCAM(-), CD31(-), FAP(+)].

2013-01-17 | E-GEOD-39396 | biostudies-arrayexpress

Expression data from fibroblasts treated with TGF-Beta

Project description:The survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease. We quantified the association of TGF-beta-activated fibroblasts with disease progression. To this end, we used as surrogates the gene expression programme upregulated by addition of TGF-beta to normal colon mucosa-derived fibroblasts (CCD-Co-18) in culture. CCD-Co-18 were seeded at 60% confluence and treated with TGF-Î²1. Gene expression profiles were measured in duplicate using HG-U133 plus 2.0. We used RMA background correction, quantile normalization and RMA summarization (Gautier et al., 2004). A TGF-Î² response signature was obtained by selecting genes with limma P-value < 0.05 and at least two fold up-regulation in TGF-Î² treated fibroblasts.

2013-01-17 | E-GEOD-39394 | biostudies-arrayexpress

Novel prognostic implications of complement activation in the tumor microenvironment for de novo metastatic BRAF V600E mutant colorectal cancer

Project description:Prognosis of metastatic BRAF V600E mutant colorectal cancer (CRC) is poor, and the prognostic implications of immune contextures in the tumor microenvironment (TME) for CRC remain elusive. Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.

2022-11-08 | GSE211576 | GEO

Targeting metabolism to improve immunotherapy in GSNOR-deficient colorectal cancer

Project description:Colorectal cancer (CRC) is the third most diagnosed type of cancer and the second leading cause of cancer death worldwide. Despite the increasing knowledge of CRC molecular biology and the development of new targeted therapies, its high heterogeneity hampers the efficacy of current treatments. Thus, there is a pressing need to identify new effective therapeutic targets and improve immune therapies for these patients. In this regard, S-nitrosoglutathione reductase (GSNOR) is a denitrosylase enzyme that has been suggested to play a tumour suppressor role, although the mechanisms responsible are still largely unclear. Therefore, the main objective of this project was to understand the role of GSNOR in CRC tumorigenesis and its therapeutic implications. Firstly, we classified CRC tumours as GSNOR-high or low according to their GSNOR expression as assessed by immunohistochemistry (IHC). Accordingly, we found that GSNOR deficiency was associated with worse prognosis factors such as a larger tumour size at diagnosis, higher TNM stage, higher grade of tumour budding (TB), the CMS4 subtype, lower expression of the intestinal differentiation markers CDX2 and AE1/AE3 cytokeratin and a worse progression free survival (PFS) and overall survival (OS). We next investigated the differences in gene expression between CRC GSNOR-high and low tumours, uncovering significant alterations in metabolism and immune system pathways. Hence, GSNOR-deficient tumours were characterized by immune suppressive features and a dysregulation of their metabolism, favouring other metabolic pathways than OXPHOS.

2024-04-13 | GSE263844 | GEO

Expression profiles of cell populations purified from human CRC (3 ways)

Project description:The survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease. We purified by FACS [CD45(+),Epcam(-)], [CD45(-) Epcam(+)] and [CD45(-) Epcam(-)] cell populations from fresh CRC samples and assessed their gene expression profiles Freshly obtained tumors from CRC patients (n=8) treated at Hospital del Mar (Barcelona, Spain) were minced and incubated with 0.1% Hyaluronidase and 0.1% Collagenase 1A. Pieces were then homogenized. Enzymatic reaction was stopped by adding 10% FBS and single cells were collected by sequential filtering. Cells were resuspended in Ammonium Chloride (0.15M) to lyse erythrocytes. Cells were stained with anti-hEpcam/TROP1-APC and anti-CD45-PE conjugated antibody. Dead cells were labeled with Propidium Iodide. Fluorescence Activated Cell Sorting (FACS) was used to separate cells.

2013-01-17 | E-GEOD-39395 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data