Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genomic signatures of platinum re-sensitization in ovarian cancer [RNA-Seq]

ABSTRACT: Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in ovarian cancer. A multi-institutional randomized clinical trial compared a regimen of a DNA methyl transferase (DNMT) inhibitor guadecitabine and carboplatin to physician’s choice chemotherapy for patients with recurrent platinum resistant ovarian cancer. Tumor biopsies or malignant ascites were collected at day 1 of cycle 1 (pre-guadecitabine) and after two cycles of treatment (post-decitabine). The goal of the current study was to analyze guadecitabine-induced DNA methylation and gene expression changes and correlate pretreatment levels with clinical outcomes. Epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450) and RNA sequencing revealed extensive methylation and gene expression changes induced by guadecitabine in ovarian tumors. Ninety-four gene promoters were significantly hypomethylated after treatment with guadecitabine and 949 genes were differentially expressed in pre vs. post-treatment tumors. Pathways associated with immune reactivation and DNA repair were significantly altered by guadecitabine treatment. Expression levels of 1155 genes involved in 25 networks on day 1 of cycle 1 correlated with progression free survival. Increased expression of selected genes (e.g. DOK2, miR193a) silenced through promoter methylation restored platinum sensitivity in ovarian cancer cells. Together, these results support that guadecitabine altered DNA methylation and expression of genes and gene networks correlate with re-sensitization to carboplatin in ovarian cancer patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102118 | GEO | 2018/06/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Methylomic signatures of platinum re-sensitization in ovarian cancer [Illumina HumanMethylation450 BeadChip]

Project description:Epigenetic changes, particularly DNA methylation aberrations have been implicated in acquired resistance to platinum in ovarian cancer. A multi-institutional randomized clinical trial compared a regimen of a DNA methyl transferase (DNMT) inhibitor guadecitabine and carboplatin to physician’s choice chemotherapy for patients with recurrent platinum resistant ovarian cancer. Tumor biopsies or malignant ascites were collected at day 1 of cycle 1 (pre-guadecitabine) and after two cycles of treatment (post-decitabine). The goal of the current study was to analyze guadecitabine-induced DNA methylation and gene expression changes and correlate pretreatment levels with clinical outcomes. Epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450) and RNA sequencing revealed extensive methylation and gene expression changes induced by guadecitabine in ovarian tumors. Ninety-four gene promoters were significantly hypomethylated after treatment with guadecitabine and 949 genes were differentially expressed in pre vs. post-treatment tumors. Pathways associated with immune reactivation and DNA repair were significantly altered by guadecitabine treatment. Expression levels of 1155 genes involved in 25 networks on day 1 of cycle 1 correlated with progression free survival. Increased expression of selected genes (e.g. DOK2, miR193a) silenced through promoter methylation restored platinum sensitivity in ovarian cancer cells. Together, these results support that guadecitabine altered DNA methylation and expression of genes and gene networks correlate with re-sensitization to carboplatin in ovarian cancer patients.

2018-06-05 | GSE102119 | GEO

Methylation analysis of samples from a phase II clinical trial of decitatbine in combination with carboplatin in patients with recurrent, platinum resistant epithelial ovarian cancer

Project description:Genome wide DNA methylation profiling of blood and biopsy samples from recurrent, platinum resistant epithelial ovarian cancer patients before and after treatment of decitabine in combination with carboplatin. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in PBMC (14 paired samples), tumor (8 paired samples) and ascites (6 paired samples).

2011-09-02 | GSE31826 | GEO

Methylation analysis of samples from a phase II clinical trial of decitatbine in combination with carboplatin in patients with recurrent, platinum resistant epithelial ovarian cancer

2011-09-01 | E-GEOD-31826 | biostudies-arrayexpress

Gene expression analysis of samples from a phase II clinical trial of decitatbine in combination with carboplatin in patients with recurrent, platinum resistant epithelial ovarian cancer patients

Project description:Gene expression (by Affymetrix GeneChip Human 1.0ST) profiling of biopsy samples from recurrent, platinum resistant epithelial ovarian cancer patients before and after treatment of decitabine in combination with carboplatin. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in PBMC (14 paired samples), tumor (8 paired samples) and ascites (6 paired samples) (GSE31826).

2014-03-04 | GSE55410 | GEO

Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy

Project description:Platinum chemoresistance results in disease recurrence in patients with high-grade serous ovarian cancer (HGSOC). Recent advances in the treatment of solid tumours using checkpoint inhibitor immunotherapy has not benefited platinum-resistant HGSOC. Epigenetic silencing of genes involved in triggering cell death and apoptosis in HGSOC is known to occur via hypermethylation during development of platinum resistance. DNA methyltransferase (DNMT) inhibitors block methylation from occurring and allow silenced genes to be expressed. In ovarian cancer, DNMT inhibitors alter the epigenome and transcriptome of the tumours, which primarily affected expression of immune reactivation pathways. We aimed to determine the epigenome and transcriptome response to sequential treatment of HGSOC cells with DNMTi followed by standard-of-care carboplatin.

2022-02-02 | GSE168225 | GEO

Sequential azacitidine and carboplatin can prime high-grade serous ovarian cancer to respond to checkpoint inhibitor immunotherapy.

2022-02-02 | GSE169617 | GEO

Transcription profiling of human epithelial ovarian cancer cell lines treated with Carboplatin reveals carboplatin induced gene expression changes in vitro are prognostic of survival - time series

Project description:We performed a time-course microarray experiment to define the transcriptional response to carboplatin in vitro, and to correlate this with clinical outcome in epithelial ovarian cancer (EOC). RNA was isolated from carboplatin and control-treated 36M2 ovarian cancer cells at several time points, followed by oligonucleotide microarray hybridization. Carboplatin induced changes in gene expression were assessed at the single gene as well as at the pathway level. Clinical validation was performed in publicly available microarray datasets using disease free and overall survival endpoints. Time-course and pathway analyses identified 317 genes and 40 pathways (designated time-course and pathway signatures) deregulated following carboplatin exposure. Both types of signatures were validated in two separate platinum-treated ovarian and NSCLC cell lines using published microarray data. Expression of time-course and pathway signature genes distinguished between patients with unfavorable and favorable survival in two independent ovarian cancer datasets. Among the pathways most highly induced by carboplatin in vitro, the NRF2, NF-kB, and cytokine and inflammatory response pathways were also found to be upregulated prior to chemotherapy exposure in poor prognosis tumors. Experiment Overall Design: we treated the 36M2 cell line with carboplatin 100Î¼M or vehicle-control for 24hrs and cells were harvested and processed for RNA isolation at 24, 30 and 36hrs after treatment.

2009-01-14 | E-GEOD-13525 | biostudies-arrayexpress

Gene expression analysis of samples from a phase II clinical trial of decitatbine in combination with carboplatin in patients with recurrent, platinum resistant epithelial ovarian cancer patients

2014-03-04 | E-GEOD-55410 | biostudies-arrayexpress

Promoter CpG island methylation data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines.

2009-04-17 | GSE15373 | GEO

Promoter CpG island methylation data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines.

Project description:Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, and investigate the DNA methylation alterations associated with cisplatin resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation microarray analyses. We treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation analyses by differential methylation hybridization (DMH) using a customed 44K promoter CGI microarray.

2010-06-19 | E-GEOD-15373 | 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