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| Status |
Public on Jun 05, 2018 |
| Title |
Genomic signatures of platinum re-sensitization in ovarian cancer [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
93 samples are analyzed, including tumor samples collected from patients with platinum resistant ovarian cancer before treated by guadecitabine and after treated by guadecitabine.
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| Contributor(s) |
Fang F, Nephew KP, Matei D |
| Citation(s) |
29229600 |
| |
| Submission date |
Aug 01, 2017 |
| Last update date |
Aug 08, 2022 |
| Contact name |
Kenneth Nephew |
| E-mail(s) |
knephew@indiana.edu
|
| Organization name |
Indiana University
|
| Street address |
1001 E 3rd st.
|
| City |
Bloomington |
| State/province |
IN |
| ZIP/Postal code |
47405 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (92)
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| This SubSeries is part of SuperSeries: |
| GSE102120 |
Genomic and Epigenomic Signatures of Platinum Re-sensitization in ovarian cancer |
|
| Relations |
| BioProject |
PRJNA396733 |
| SRA |
SRP114518 |
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