Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-Cell transcriptome analysis revealed the heterogeneity and microenvironment of gastrointestinal stromal tumors

ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of human gastrointestinal (GI) tract. In this study, we performed single cell RNA sequencing on intra- and peri- tumor tissues from GIST patients in an aim to discover the heterogeneity of tumor cells in GIST and their interactions with other cells. We found 4 predominating cell types in GIST tumor tissue, including T cells, macrophages, tumor cells and NK cells. Tumor cells could be clustered into two groups: one was highly proliferating and associated with high risk of metastasis; the other seemed “resting” and associated with low risk. Their clinical relevance and prognostic values were confirmed by RNA-seq of 65 GIST samples. T cell was the largest cell type in our single cell data. Two groups of CD8+ effector memory (EM) cells were in the highest clonal expansion and performed the highest cytotoxicity but also the most exhausted among all T cells. A group of macrophages were found polarized to possess both M1 and M2 signatures, and increased along with tumor progression. Cell to cell interaction analysis revealed that adipose endothelial cells had high interactions with tumor cells to facilitate their progression. Macrophages were at the center of tumor microenvironment, recruiting immune cells to the tumor cite and having most interactions with both tumor and non-tumor cells. In conclusion, we obtained an overview of GIST microenvironment and revealed the heterogeneity of each cell type and their relevance to risk classifications, which provided novel theoretical basis for learning and curing GISTs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162115 | GEO | 2021/01/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

MiRNAs array after SH3BP2 silencing in Gastrointestinal stromal tumor cells

Project description:Silencing of the adaptor SH3BP2 impairs Gastrointestinal stromal tumors growth through miRNAs We dissected SH3BP2 pathway in Gastrointestinal Stromal Tumor cells (GIST) performing a miRNA array in SH3BP2-silenced GIST cells

2022-09-23 | GSE213777 | GEO

MOZ and Menin-MLL Complexes are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor [ChIP-seq and CUT&Tag]

Project description:Gastrointestinal stromal tumor (GIST) is commonly characterized by activating mutations in the receptor tyrosine kinase KIT. Tyrosine kinase inhibitors are the only approved therapy for GIST, and other complementary treatment strategies are urgently needed. As GIST both lacks oncogene amplification and relies upon an established network of transcription factors, we hypothesized that unique chromatin modifying enzymes are essential in orchestrating the GIST epigenome. Here, we identified through genome-wide CRISPR screening that MOZ and Menin-MLL chromatin regulatory complexes are cooperative and unique dependencies in GIST. These complexes were enriched at GIST-relevant genes and regulated their transcription. Inhibition of MOZ and Menin-MLL complexes decreased GIST cell proliferation by disrupting interactions with transcriptional regulators, such as DOT1L. Menin inhibition caused significant reductions in tumor burden in xenograft models, with superior effects observed in combination with imatinib. These results define unique chromatin regulatory dependencies in GIST and identify therapeutic strategies for clinical application.

2022-05-02 | GSE172152 | GEO

MOZ and Menin-MLL Complexes are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor [RNA-seq]

2022-05-02 | GSE172153 | GEO

Kinome Profiling of Gastrointestinal Stromal Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies Wee1 as a Candidate Therapeutic Target

Project description:Purpose: Management of gastrointestinal stromal tumor (GIST) has been revolutionized by the identification of activating mutations in KIT and PDGFRA and the clinical application of receptor tyrosine kinase (RTK) inhibitors in the advanced disease setting. Stratification of GIST into molecularly defined subsets provides insight into clinical behavior and response to approved targeted therapies. Although these RTK inhibitors are effective in the majority of GIST, resistance to these agents remains a significant clinical obstacle. Development of effective treatment strategies for refractory GIST requires identification of novel targets to provide additional therapeutic options. Global kinome profiling has the potential to identify critical signaling networks and reveal protein kinases that are essential in GIST. Experimental Design: Using Multiplexed Inhibitor Beads and Mass Spectrometry paired with a super-SILAC kinome standard, we explored the majority of the kinome in GIST specimens from three GIST subtypes (KIT-mutant, PDGFRA-mutant and succinate dehydrogenase-deficient GIST) to identify novel kinase targets. In vitro and in vivo studies were performed to evaluate the utility of targeting the identified kinases in GIST. Results: Kinome profiling revealed distinct signatures in three GIST subtypes. PDGFRA-mutant GIST had elevated tumor associated macrophage (TAM) kinases and immunohistochemical analysis confirmed increased TAMs present in these tumors. Kinome profiling with loss-of-function assays revealed a significant role for G2-M tyrosine kinase, Wee1, in GIST survival. In vitro and in vivo studies revealed significant efficacy of MK-1775 (Wee1 inhibitor) in combination with avapritinib in both KIT and PDGFRA-mutant GIST cell lines, as well as notable efficacy of MK-1775 as a single agent in the PDGFRA-mutant line. Conclusions: These studies provide strong preclinical justification for the use of MK-1775 in GIST.

2021-09-09 | PXD020720 | Pride

Expression Profiling Identifies Key Genes in GIST Patients with Liver Metastasis

Project description:GIST (gastrointestinal stromal tumor) is the most prominent mesenchymal neoplasms of the gastrointestinal tract, and liver is the most common metastasis site for GIST. The molecular mechanism leading to liver metastasis of GIST is currently unclear. With the goal of revealing the underlying mechanism, we performed whole-genome gene expression profiling in 18 pairs of RNA samples comprised of liver metastasis tissues and corresponding non-tumor tissues. To reveal the underlying mechanism leading to liver metastasis of GIST

2023-03-31 | GSE225819 | GEO

Gastrointestinal stromal tumor GIST: gene expresssion and ChIP analyses

Project description:This SuperSeries is composed of the following subset Series: GSE19396: ETV1 knockdown in GIST cell lines GSE22433: Imatinib Treatment of GIST882 GSE22441: Mapping of ETV1 genomic binding sites in gastrointestinal stromal tumor (GIST). Refer to individual Series

2010-10-14 | E-GEOD-22852 | biostudies-arrayexpress

Distinctive gene expression patterns in gastrointestinal stromal tumors identified with cDNA arrays

Project description:Gastrointestinal stromal tumors (GIST) are phenotypically and clinically heterogeneous mesenchymal tumors. Using the cDNA array technique, we analyzed the gene expression profiles of 22 GIST and 7 non-neoplastic gastrointestinal smooth muscle specimens, in order to detect molecular differences between GIST and non-neoplastic tissue, and to detect differences between GIST of various phenotypic and clinical subgroups. As a result, we found 796 differentially expressed genes and ESTs between GIST and smooth muscle tissue, including promising new candidate genes for the pathogenesis of GIST. Furthermore, we identified differences in gene expression between GIST of different site, size, and immunohistochemical expression of CD34 and SMA. Our data show that alterations in gene expression are associated with morphologically and clinically detectable features of GIST and provide new aspects for the understanding of these tumors. Keywords = Gastrointestinal Stromal Tumor (GIST)

2003-04-10 | E-GEOD-112 | biostudies-arrayexpress

250K SNP array data for 40 high-grade myogenic cancers

Project description:Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS), and leiomyosarcoma (LMS), feature myogenic differentiation. Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in nonneoplastic and benign counterparts for GIST, RMS and LMS, and the DMD deletions inactivate larger dystrophin isoforms, including 427kDa dystrophin, while preserving expression of an essential 71kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence, and invadopodia formation, and dystrophin inactivation was found in 96%, 100%, and 62% of metastatic GIST, embryonal RMS, and LMS, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in treatment of cancer. High molecular weight genomic DNA was isolated from 40 high-grade myogenic cancers (including 7 normal tissue/tumor pairs and 33 additional tumors) using QIAamp DNA Mini Kit (QIAGEN) and analyzed by Affymetrix 250K SNP array.

2014-05-02 | E-GEOD-53021 | biostudies-arrayexpress

Distinctive gene expression patterns in gastrointestinal stromal tumors identified with cDNA arrays

2003-04-10 | GSE112 | GEO

GIST proteome dataset(Proteomic Maps of Human Gastrointestinal Stromal Tumor Subgroups)

Project description:Gastrointestinal stromal tumor (GIST) is a common sarcoma of gastrointestinal tract (GIT) with high metastatic and recurrence rates, but the proteomic features are still less understood. Here we performed systematic quantitative proteome profiling of GIST from 13 patients classified into very low/low, intermediate and high risk subgroups. An extended cohort of GIST (n = 131) was used for immunohistochemical validation of proteins of interest. In total, 10064 proteins were quantified, covering 61% of the GIT transcriptome from The Human Protein Altas. Out of the 10064 quantified proteins, 4938 proteins were observed in all 13 cases with 518 proteins upregulated and 190 proteins downregulated in tumorous tissues independent of risk rating. Pathway analysis showed that the downregulated proteins were mostly enriched in metabolic pathway, while the upregulated proteins mainly belonged to spliceosome pathway. In addition, 131 proteins showed differentially expressed patterns among GIST subgroups with statistical significance. The 13 GIST cases were classified into 3 subgroups perfectly based on the expression of these proteins. The molecular phenotypes of oncoproteins, tumor suppressors, phosphatase and kinases were summarized, and some important molecules were observed. Immunohistochemical analysis of two phosphatases PTPN1 (n = 117) and PPP2CB (n=113) revealed that the GIST patients with high PTPN1 had low chances of developing metastasis, and the expression of PPP2CB was likely to be associated with GIST risk. Collectively, this work provides valuable information for understanding the inherent biology and evolution of GIST.

2019-01-29 | PXD011299 |

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