Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiles of cells from PDOs of normal colon and colorectal cancers [RNA-Seq]

ABSTRACT: Phenotypic plasticity is a major driver of cancer progression, metastasis, and treatment resistance. However, the principles governing human cancer plasticity associated with poor prognosis remain poorly understood due to the lack of in vitro models. Here we identified a unique cancer cell state at single-cell resolution to predict poor prognosis across several human cancers with different clinical features, especially colorectal cancer (CRC) progression and metastasis, named the poor prognostic plastic state (PPPS). A functional patient-derived organoid xenograft (PDOX) model was developed to capture and maintain the PPPS in CRC. With a marker gene of MSLN (encoding mesothelin), this model was used to validate the role of the PPPS in promoting CRC metastasis. Moreover, precise manipulation of human cancer plasticity through the PPPS allows us to identify small-molecule inhibitors of non-canonical IKKs to promote malignancy, with clinical implications for targeting the PPPS to prevent CRC progression and metastasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261004 | GEO | 2024/04/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Single-cell gene expression profiles of cells from colorectal cancer and chemically induced PDOs [scRNA-Seq]

Project description:Phenotypic plasticity is a major driver of cancer progression, metastasis, and treatment resistance. However, the principles governing human cancer plasticity associated with poor prognosis remain poorly understood due to the lack of in vitro models. Here we identified a unique cancer cell state at single-cell resolution to predict poor prognosis across several human cancers with different clinical features, especially colorectal cancer (CRC) progression and metastasis, named the poor prognostic plastic state (PPPS). A functional patient-derived organoid xenograft (PDOX) model was developed to capture and maintain the PPPS in CRC. With a marker gene of MSLN (encoding mesothelin), this model was used to validate the role of the PPPS in promoting CRC metastasis. Moreover, precise manipulation of human cancer plasticity through the PPPS allows us to identify small-molecule inhibitors of non-canonical IKKs to promote malignancy, with clinical implications for targeting the PPPS to prevent CRC progression and metastasis.

2024-04-17 | GSE261012 | GEO

Transcriptome-wide identification of transcripts regulated by PHF5A in colorectal cancer cells

Project description:Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here we demonstrated that PHF5A, a component of U2 snRNPs, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS, and established PHF5A as potential therapeutic target.

2021-07-16 | GSE180042 | GEO

Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Bulk RNA-Seq]

Project description:Peritoneal carcinomatosis (PC) originating from colorectal cancer (CRC) is associated with a poor prognosis and rapid disease progression. Metastasis is the major cause of death in patients with CRC whereas primary locoregionally circumscribed tumors are mostly curable. Due to the lack of appropriate and realistic mouse models for metastasis of CRC until recently, the research about metastasis of these tumors and possible therapeutic options is still in its infancy. With the establishment of murine CRC tumor organoids, mouse models were established which realistically mimic the process of tumor cell metastasis to the liver and the lung. However, to date no appropriate model for PC is described. Here, we establish a realistic model for peritoneal metastasis of colorectal cancer upon surgical transplantation of tumor organoids into the cecum wall. This mouse model for PC recapitulates human PC which makes it an ideal model for research of the biology of metastasis of colorectal cancer to the peritoneal cavity and for its usage for preclinical drug screening as well as for the evaluation of new therapeutic approaches which are highly needed in clinical reality.

2022-06-27 | GSE202454 | GEO

E-selectin Affinity Glycoproteomics Reveals Neuroendocrine Proteins and the Secretin Receptor as a Poor Prognosis Signature in Colorectal Cancer

Project description:Colorectal cancer (CRC) cells express glycoproteins with sialylated Lewis antigens (sLe), crucial for metastasis via E-selectin binding. However, these glycoepitopes lack cancer specificity, and E-selectin-targeted glycoproteins are unknown. Here we established a framework for identifying metastasis-linked glycoproteoforms for precision oncology. We found that over 70% of colorectal tumours overexpressed sLeA/X, yet without association with metastasis or survival. This prompted deeper exploration on the sialoglycoproteome of metastatic tumours. Nearly 600 glycoproteins were identified using E-selectin affinity enrichment and mass spectrometry, significantly broadening our understanding of potential metastasis-related glycoproteins. This glycoproteome was linked to cell adhesion, active transport of molecules and ions across the plasma membrane, oncogenic pathways, angiogenesis, and, unexpectedly, neuroendocrine functions. Employing an in-house algorithm for targetability prioritization, the less studied secretin receptor (SCTR) emerged as a top-ranked glycoprotein. The screening of tumours confirmed SCTR's association with poor prognosis and metastasis. N-glycosylation carrying sLe antigens added cancer specificity to SCTR. Prognostic links were reinforced by TCGA-based investigations. In summary, SCTR, a relatively unknown CRC glycoprotein, holds potential as a biomarker of poor prognosis and as a E-selectin ligand, suggesting an unforeseen role in metastasis warranting confirmation. Future investigations should also focus on this glycoproteoforms’ biological foreseeing clinical applications.

2024-11-11 | PXD054727 | Pride

Orthotopic CRC organoid transplantation in mice: A novel model for the study and treatment of peritoneal carcinomatosis [Whole-tumor 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 tumor cells and the corresponding tumor 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 tumor epithelium, stroma and immune cells. Interestingly, we found an intercellular site-specific network of cancer associated fibroblasts and tumor 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 | GSE220506 | GEO

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

2024-01-10 | GSE220175 | GEO

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

FGF19 facilitates colorectal cancer metastasis through FGFR4-ERK-NF-κB signaling pathway

Project description:Globally, colorectal cancer(CRC) is the third most common malignancy. In recent years, despite the emergence of new screening and treatment strategies, the prognosis of CRC remains poor and distant metastasis remains a major obstacle to the treatment of CRC. Therefore, it is significant to explore new diagnostic and prognostic markers and therapeutic targets. Fibroblast growth factor 19(FGF19) has been reported to promote tumor invasion of CRC. However, the exact mechanism is still unclear.

2023-11-20 | GSE161963 | GEO

Stromal contribution to expression signatures of colorectal cancer (CRC tumor)

Project description:We noticed that a recently identified poor prognosis stem/serrated molecular subtype of colorectal cancer (CRC) is characterized by up-regulation of transcripts known to be also expressed by stromal cells. To better define the origin of such transcripts, we analyzed RNAseq and microarray datasets from CRC mouse xenografts, where human cancer cells are supported by murine stroma. The analysis revealed that mRNA levels of stem/serrated subtype genes are mostly due to stromal expression, even when the stromal fraction is below 5%. Indeed, a classifier based on genes exclusively expressed by cancer-associated fibroblasts was significantly associated, in multiple datasets, to poor prognosis of CRC and to radioresistance of rectal cancer. Tumor Matched with Corresponding PDX

2014-05-01 | E-GEOD-56695 | biostudies-arrayexpress

The underlying mechanism of SCNAs-induced lncRNA LOC101927668 overexpressoin facilitating colorectal cancer progression

Project description:Somatic copy number alterations (SCNAs) are pivotal in cancer progression and patient prognosis. Dysregulated long non-coding RNAs (lncRNAs), modulated by SCNAs, significantly impact tumorigenesis, including colorectal cancer (CRC). Nonetheless, the functional significance of lncRNAs induced by SCNAs in CRC remains largely unexplored. In this study, we elucidate that the overexpression of LOC101927668, driven by SCNAs, facilitates CRC proliferation and metastasis by recruiting hnRNPD, thus perturbing the RBM47/P53/P21 signaling pathway.

2024-10-15 | GSE268122 | GEO

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