Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deciphering the Tumor Immune Microenvironment of Imatinib-Resistance in Advanced Gastrointestinal Stromal Tumors at Single-Cell Resolution

ABSTRACT: The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming.

ORGANISM(S): Homo sapiens

PROVIDER: GSE254762 | GEO | 2024/03/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular comparison of imatinib-naïve and resistant gastrointestinal stromal tumors: differentially expressed microRNAs and mRNAs

Project description:Despite the success of imatinib in advanced gastrointestinal stromal tumor (GIST) patients, 50% of the patients experience resistance within two years of treatment underscoring the need to get better insight into the mechanisms conferring imatinib resistance. Here the microRNA and mRNA expression profiles in primary (imatinib-naïve) and imatinib-resistant GIST were examined. Fifty-three GIST samples harboring primary KIT mutations (exon 9; n=11/exon 11; n=41/exon 17; n=1) and comprising imatinib-naïve (IM-n) (n=33) and imatinib-resistant (IM-r) (n=20) tumors, were analyzed. The microRNA expression profiles were determined and from a subset (IM-n, n=14; IM-r, n=15) the mRNA expression profile was established. Ingenuity pathway analyses were used to unravel biochemical pathways and gene networks in IM-r GIST. Thirty-five differentially expressed miRNAs between IM-n and IM-r GIST samples were identified. Additionally, miRNAs distinguished IM-r samples with and without secondary KIT mutations. Furthermore 352 aberrantly expressed genes were found in IM-r samples. Pathway and network analyses revealed an association of differentially expressed genes with cell cycle progression and cellular proliferation thereby implicating genes and pathways involved in imatinib resistance in GIST. Differentially expressed miRNAs and mRNAs between IM-n and IM-r GIST were identified. Bioinformatic analyses provided insight into the genes and biochemical pathways involved in imatinib-resistance and highlighted key genes that may be putative treatment targets.

2019-06-12 | GSE132542 | GEO

microRNA expression signatures of imatinib-treated and non-treated gastrointestinal stromal tumors

2015-08-01 | GSE63159 | GEO

Small RNA expression signatures of gastrointestinal stromal tumors: associations to imatinib resistance and patient outcome

2013-04-10 | GSE45901 | GEO

Expression Data from Gastrointestinal Stromal Tumor (GIST) Cell Lines

Project description:Activating mutations in either KIT or PDGFRA are present in approximately 90% of gastrointestinal stromal tumors (GISTs). Although treatment with the KIT and PDGFR inhibitor imatinib can control advanced disease in about 80% of GIST patients, the beneficial effect is not durable. Here, we report that ligands from the FGF family reduced the effectiveness of imatinib in GIST cells, and FGF2 and FGFR1 are highly expressed in all primary GIST samples examined. The combination of KIT and FGFR inhibition showed increased growth inhibition in imatinib-sensitive GIST cell lines in the presence or absence of added FGF2 in vitro, and delayed tumor regrowth in vivo. In addition, inhibition of mitogen-activated protein kinase (MAPK) signaling by imatinib was not sustained in GIST cells. An extracellular signal-regulated kinase (ERK) rebound occurred through activation of FGF signaling, and was repressed by FGFR1 inhibition. Downregultation of Sprouty proteins played a role in the imatinib-induced feedback activation of FGF signaling in GIST cells. We used micorarrays to quantify the gene expression levels in GIST cell lines. Four GIST cell lines were split and cultured overnight. Cells were harvested for RNA extraction and hybridization on Affymetrix U133plus2 microarrays.

2015-01-08 | E-GEOD-64762 | biostudies-arrayexpress

Expression Data from Gastrointestinal Stromal Tumor (GIST) Cell Lines

2015-01-08 | GSE64762 | GEO

microRNA expression signatures of imatinib-treated and non-treated gastrointestinal stromal tumors

Project description:We performed microRNA expression profiling in a series of fresh-frozen neoadjuvantly imatinib-treated and non-treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed microRNAs among imatinib-treated and non-treated groups were identified using SAM analysis. Agilent microarray platform with probes matching 903 human microRNAs was used to determine miRNA expression profiles in 34 GISTs (19 imatinib-treated and 15 non-treated). Re-analysis of GSE45901 for 17 imatinib-treated GISTs. To validate the microarray platform, the expression levels of selected microRNAs were evaluated using qRT-PCR.

2015-08-01 | E-GEOD-63159 | biostudies-arrayexpress

Small RNA expression signatures of gastrointestinal stromal tumors: associations to imatinib resistance and patient outcome

Project description:We performed miRNA expression profiling in a series of fresh-frozen neoadjuvantly imatinib treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed miRNAs among imatinib-resistant and imatinib-sensitive groups were identified using SAM analysis. Agilent microarray platform with probes matching 903 human miRNAs was used to determine miRNA expression profiles in 17 GISTs (imatinib-sensitive and 7 imatinib-resistant). To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.

2013-04-10 | E-GEOD-45901 | biostudies-arrayexpress

Integrated Profiling and Immunohistochemistry Analyses Link circ-BRIP1, circ-EPHB4 and Their Host Genes with Imatinib Resistance in Gastrointestinal Stromal Tumors

Project description:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The majority of GIST patients eventually develop resistance to imatinib therapy. To identify the responsible mechanisms, we investigated the differentially expressed mRNAs and circRNAs in imatinib-resistant GISTs using SBC ceRNA microarrays. We found that 107 mRNAs and 521 circRNAs were significantly differentially expressed between imatinib-naïve and imatinib-resistant GIST tissue samples. qRT-PCR analyses validated that circ-BRIP1, circ-EPHB4 and circ-RECQL4 and their host genes were upregulated in imatinib-resistant GISTs, and circ-BRIP1, circ-EPHB4, and RECQL4 were associated with imatinib resistance, tumor relapse and progression, and metastasis in GIST patients. The expression levels of circ-BRIP1, circ-EPHB4 and their host genes were also evaluated using TMAs with 150 human GISTs. The expression level of EPHB4 was significantly increased in high-grade GISTs in comparison to low-grade GISTs and correlated with imatinib resistance. Specifically, we first developed a method for high-throughput analysis of the expression of differentially expressed circRNAs by ISH-IHC in a set of FFPE-tissue microarrays in GIST. Our results also suggested a possible role for circ-BRIP1, circ-EPHB4, and their host genes in the progression of GISTs.

2024-11-01 | GSE188700 | GEO

The effect of imatinib therapy on tumor associated macrophages (TAMs) in murine gastrointestinal stromal tumor (GIST)

Project description:The gene expression profile of TAMs sorted from vehicle control tumors in GIST mice (Sommer et al, PNAS 2003) was compared to TAMs sorted from mice after 2 weeks of imatinib therapy The Affymetrix Mouse Genome 430A 2.0 platform was used

2013-11-20 | GSE51698 | GEO

Genome wide analysis of mouse gastrointestinal stromal tumors (GIST) in a mouse model of spontaneous GIST.

Project description:Analysis of mouse GIST tumors at the gene expression level. The purpose of the study was to identify immunomodulatory genes in mouse GIST tumors after in vivo treatment with the specific tyrosine kinase inhibitor imatinib mesylate. Total RNA obtained from mouse GIST tumors after in vivo treatment with imatinib or vehicle control injected intraperitoneally.

2011-12-31 | E-GEOD-30416 | 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