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Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers

ABSTRACT: Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers

PROVIDER: PRJNA971167 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24491800.fastq.gz	Fastqsanger.gz
	SRR24491801.fastq.gz	Fastqsanger.gz
	SRR24491802.fastq.gz	Fastqsanger.gz
	SRR24491803.fastq.gz	Fastqsanger.gz
	SRR24491804.fastq.gz	Fastqsanger.gz

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Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers

Project description:To investigate in situ-in vitro molecular correspondence and the relationship between in vitro and patient response to temozolomide (TMZ)

2023-08-23 | GSE232173 | GEO

Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers.

Project description:BackgroundPatient-derived glioma stem-like cells (GSCs) have become the gold-standard in neuro-oncological research; however, it remains to be established whether loss of in situ microenvironment affects the clinically-predictive value of this model. We implemented a GSC monolayer system to investigate in situ-in vitro molecular correspondence and the relationship between in vitro and patient response to temozolomide (TMZ).MethodsDNA/RNA-sequencing was performed on 56 glioblastoma tissues and 19 derived GSC cultures. Sensitivity to TMZ was screened across 66 GSC cultures. Viability readouts were related to clinical parameters of corresponding patients and whole-transcriptome data.ResultsTumour DNA and RNA sequences revealed strong similarity to corresponding GSCs despite loss of neuronal and immune interactions. In vitro TMZ screening yielded three response categories which significantly correlated with patient survival, therewith providing more specific prediction than the binary MGMT marker. Transcriptome analysis identified 121 genes related to TMZ sensitivity of which 21were validated in external datasets.ConclusionGSCs retain patient-unique hallmark gene expressions despite loss of their natural environment. Drug screening using GSCs predicted patient response to TMZ more specifically than MGMT status, while transcriptome analysis identified potential biomarkers for this response. GSC drug screening therefore provides a tool to improve drug development and precision medicine for glioblastoma.

| S-EPMC10575865 | biostudies-literature

MGMT enhancer modulates glioma cell sensitivity to temozolomide through long-range regulations of multiple genes

Project description:Acquired resistance of temozolomide (TMZ) is one of the major obstacle of glioblastoma clinical treatment and the mechanism of TMZ resistance is still not very clear. In the presented research we show that deletion of rs16906252-associated MGMT enhancer in MGMT negative glioma cells induced increase sensitivity to temozolomide and combination of RNA-seq and Capture HiC identified several long-range target genes of rs16906252-associated MGMT enhancer. In addition, HiC data shows alterations of chromatin structures in glioma cells survived from high-dosage TMZ treatment and changes of TADs influence rs16906252-associated MGMT enhancer’s long-range regulations of target genes. Our study suggests rs16906252-associated MGMT enhancer regulates glioma cells’ TMZ sensitivity by long-range regulations of several target genes, which is a novel mechanism of regulation of TMZ sensitivity in glioma cells.

2020-04-02 | GSE129476 | GEO

FBXO5 degrades DOK6 to enhance cell mechanics and sensitivity to Temozolomide

Project description:stable CRISPR/Cas9 sgRNA-expression U251 cells were treated with 200nM or 1500nM temozolomide for 72 hours, and then, we screened temozolomide-resistance genes by negative selection and temozolomide-sensitive genes by positive selection

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Bivalent activity of super-enhancer RNA LINC02454 controls 3D chromatin structure and regulates glioma sensitivity to temozolomide.

Project description:Temozolomide (TMZ) resistance of glioma cells is currently a critical problem in glioma clinical treatment. In this study, we reveal a bivalent function of a super-enhancer RNA LINC02454 in modulating glioma cell sensitivity to TMZ via regulation of SORBS2 and DDR expression. LINC02454 increased TMZ sensitivity by maintaining 3D chromatin structure and promoting SORBS2 expression, but paradoxically decreased TMZ sensitivity by binding to the DDR1 locus and promoting DDR1 transcription. This study proposes a new regulatory mechanism governing glioma cell sensitivity to TMZ and provides new insights that may improve therapies against glioma.

2024-01-10 | GSE229600 | GEO

FBXO5 degrades DOK6 to enhance cell mechanics and sensitivity to Temozolomide

Project description:FBXO5 degrades DOK6 to enhance cell mechanics and sensitivity to Temozolomide

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Proteomics of Temozolomide for Glioblastoma

Project description:Using the human glioblastoma cell line LN229, temozolomide was used to detect proteome changes and identify critical components regulating chemotherapy sensitivity.

2023-05-17 | PXD042080 | Pride

A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes

Project description:Temozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture HiC and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and TAD analysis based on HiC data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.

2019-01-25 | GSE125629 | GEO

Gene profile of glioblastoma cells treated with y15 and temozolomide

Project description:The gene expression profiles were identified in glioblastoma cells treated with FAK inhibitor Y15, temozolomide alone or with combination of Y15 and Temozolomide DBTRG and U87 were treated with FAK inhibitor Y15 at 10 microM for 24 h; U87 cells were treated with Temozolomide 100 microM for 24 h and Y15+temozolomide at the same dose as each agent alone

2013-01-12 | E-GEOD-43452 | biostudies-arrayexpress

Gene expression profiling predicts sensitivity of chronic lymphocytic leukemia cells to dasatinib

Project description:Gene expression profiling predicts sensitivity of chronic lymphocytic leukemia cells to dasatinib

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