Ontology highlight
ABSTRACT:
PROVIDER: PRJNA684350 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13239800.fastq.gz | Fastqsanger.gz | |||
| SRR13239801.fastq.gz | Fastqsanger.gz | |||
| SRR13239802.fastq.gz | Fastqsanger.gz | |||
| SRR13239803.fastq.gz | Fastqsanger.gz | |||
| SRR13239798.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:Multiomic analysis identifies CPT1A as a potential therapeutic target in platinum-refractory high grade serous ovarian cancer
| PRJNA685120 | ENA
Project description:In the present project, in order to explore the molecular basis of platinum resistance and further determine potential biomarkers and therapeutic targets for high-grade serous ovarian cancer (HGSOC), we conducted a comparative proteomic analysis to identify the differentially expressed proteins between tumor tissues from platinum-sensitive and platinum-resistant HGSOC patient groups.
2021-09-30 | PXD028225 |
Project description:Platinum-based chemotherapies are widely used anti-cancer drugs. Tumor resistance to platinum compounds is a major determinant of patient survival, including in high grade serous ovarian cancer (HGSOC). To understand mechanisms of platinum resistance and identify potential therapeutic targets in resistant HGSOC, we generated a comprehensive, reproducible data resource comprised of dynamic (+/-carboplatin) proteomic/posttranslational modification and RNASeq profiles from HGSOC intra-patient cell line pairs derived from 3 patients before and after acquiring platinum resistance. The molecular profiles revealed extensive responses to carboplatin and differential responses between sensitive and resistant cells. Higher oxidative phosphorylation and fatty acid oxidation (FAO) pathway expression were observed in the platinum-resistant cells, which was further validated in patient-derived xenograft (PDX) models. We show that both pharmacologic inhibition and CRISPR knockout of CPT1A, which represents a rate limiting step of FAO, sensitize HGSOC cells to platinum. Thus, FAO is a candidate therapeutic target to overcome platinum resistance.
2022-01-04 | GSE163152 | GEO
Project description:In the United States, high grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy and tumor response to platinum-based chemotherapy is a major determinant of clinical outcome. Although recent efforts have dramatically improved the median survival of advanced ovarian cancer, the initial treatment of the disease has remained the same. The initial therapy includes surgery and chemotherapy and the response rate is very high (85%). Unfortunately, 15% of patients do not respond to this therapy and have platinum-refractory disease. These patients have a very short survival and there is an urgent need to identify novel pharmaceutically targetable pathways to treat these patients. We generated extensive proteomic (global, phospho, ubiquitin, acetylation, pTyr) and RNASeq-based dynamic molecular profiles (+/-carboplatin at 8 and 24 hours) from HGSOC intra-patient cell line pairs (PEA1/PEA2, PEO1/PEO4, PEO14/PEO23) derived from 3 patients before and after acquiring platinum resistance. The molecular profiles revealed a multi-faceted response to carboplatin (e.g., induction of a DNA damage response, ubiquitination of ribosomal proteins, and metabolic changes), as well as novel carboplatin-induced post-translational modifications. Higher oxidative phosphorylation (OXPHOS) and fatty acid beta-oxidation (FAO) pathway expression was observed in resistant compared with sensitive cells. These expression findings were validated via metabolite profiling of cell lines and proteomic profiling of platinum sensitive and refractory HGSOC patient derived xenograft (PDX) models. Both pharmacologic inhibition and CRISPR knockout of CPT1A, which represents the rate limiting step of FAO, sensitizes HGSOC cells to platinum. The metabolic signature identified in the cell line and PDX models is correlated with survival in a previously reported proteomic analysis of HGSOC, and thus FAO is a candidate druggable pathway to overcome platinum resistance.
2021-12-22 | PXD020764 | Pride
Project description:This study aims at correlating changes in the transcriptional state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
2020-02-11 | E-MTAB-7083 | biostudies-arrayexpress
Project description:This study aims at correlating changes in the microRNA state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
2020-02-11 | E-MTAB-7084 | biostudies-arrayexpress
Project description:To improve our understanding of the molecular basis of chemo-refractory high grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two independent validation cohorts (spanning four academic centers) and utilizing two biospecimen types (formalin-fixed paraffin-embedded and frozen tumor biopsies). As the largest and most comprehensive study of refractory ovarian cancers to date, this effort identified a 64-protein signature that predicts a subset of HGSOCs refractory to initial platinum-based therapy with high specificity and is validated in two independent patient cohorts. We also detected significant association between lack of Ch17 loss-of-heterozygosity and refractory disease. Moreover, based on protein pathway expression, five novel clusters of HGSOC were identified and validated across two independent patient cohorts, as well as in patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic targets.
2023-09-18 | PXD040742 | panorama
Project description:The impact of platinum and taxol based neoadjuvant chemotherapy on tumour-associated macrophages (TAMs) was examined by analysis of TAMs extracted from high grade serous ovarian cancer (HGSOC) samples pre and post chemotherapy.
2021-04-20 | GSE158739 | GEO
Project description:Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Currently patients are treated by surgical cytoreductive surgery with the aim of reducing tumor burden to microscopic disease followed by adjuvant combined treatment with a platinum and taxane containing chemotherapy, which affords 80% of patients an initial complete response. However, Abdominal and pelvic recurrence rates are high and response to further chemotherapy is limited. Attempts at introducing biologic therapeutic agents to improve outcome in this disease are ongoing, while prognostic or predictive biomarkers that can stratify patients for treatment are still lacking. Using transcriptome profiling of microdissected tissue samples from high-grade serous ovarian cancer patients, we identified a cancer associated fibroblast (CAF) specific gene signature. Versican, which encodes a extracellular matrix protein, was one of the identified genes which demonstrated up-regulation in cancer stroma. To investigate the function roles, signaling machanism and the effect of versican treatment on ovarian cancer cells, transcriptome profiling of versican treated OVCA433 high-grade serous ovarian cancer cells was performed. High grade serous ovarian cancer cell line OVCA433 was used. Total RNA was isolated from control samples and versican treated cancer cell samples at 48 hours post-treatment followed by cDNA synthesis, IVT and biotin labeling. Samples were then hybridized onto Affymetrix Human genome U133 plus 2.0 microarrays. For each treatment group, three independent samples were prepared for the microarray experiment.
2013-12-31 | E-GEOD-40241 | biostudies-arrayexpress
Project description:Objective: Ovarian tumors of low-malignant potential (LMP) and low-grade serous ovarian carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from that of high-grade serous ovarian carcinoma. Past studies have utilized gene expression profiles to support this theory. The objective of the current study was to identify new genes whose expression profiles in LMP ovarian tumors and low-grade ovarian carcinomas differ from that in high-grade ovarian carcinomas. Methods: We used RNA from 3 normal human ovarian surface epithelia (HOSE) and from 10 low-grade and 10 high-grade serous ovarian carcinoma samples to perform gene expression profiling. Using real-time reverse-transcription polymerase chain reaction (RT-PCR), we evaluated changes in PAX2 mRNA expression in cDNA created from RNA extracted from an independent set of ovarian tissue samples (7 LMP tumors and 17 low-grade and 23 high-grade serous carcinomas). We also examined PAX2 expression using Western blot analysis of protein extracted from a set of ovarian LMP and low- and high-grade carcinoma tissue samples. Additionally, we used immunohistochemistry (IHC) to validate PAX2 overexpression in a third independent set of paraffin ovarian tissue sections from 17 LMP tumors and 16 low- and 257 high-grade carcinomas. Results: Gene profiling revealed higher expression of PAX2 in low-grade than in high-grade ovarian carcinomas. Real-time RT-PCR demonstrated a statistically significant difference in median PAX2 mRNA expression, expressed as fold change, among ovarian LMP tumor (1837.38), low-grade (183.12), and high-grade (3.72) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian LMP and low-grade carcinoma samples but no PAX2 protein expression in high-grade carcinomas. On IHC, more LMP tumor and low-grade carcinoma samples expressed moderate to high levels of PAX2 than did high-grade ovarian carcinoma samples. The numbers of samples with strong nuclear staining was significantly higher for ovarian LMP tumors (10 of 17, p<0.001) and low-grade serous carcinomas (10 of 16, p<0.001) than for high-grade carcinomas (27 of 257). Discussion: Our identification and validation of higher PAX2 expression in ovarian LMP tumors and low-grade serous carcinomas than in high-grade carcinomas supports the two-tiered hypothesis that the first two are on a continuum and are distinct from high-grade ovarian carcinomas. PAX2 may represent a potential biomarker and future therapeutic target for individualizing chemotherapy for ovarian LMP tumors and low-grade carcinomas in the future. Experiment Overall Design: We used RNA from 3 normal human ovarian surface epithelia (HOSE) and from 10 low-grade and 10 high-grade serous ovarian carcinoma samples to perform gene expression profiling. Using real-time reverse-transcription polymerase chain reaction (RT-PCR), we evaluated changes in PAX2 mRNA expression in cDNA created from RNA extracted from an independent set of ovarian tissue samples (7 LMP tumors and 17 low-grade and 23 high-grade serous carcinomas). We also examined PAX2 expression using Western blot analysis of protein extracted from a set of ovarian LMP and low- and high-grade carcinoma tissue samples. Additionally, we used immunohistochemistry (IHC) to validate PAX2 overexpression in a third independent set of paraffin ovarian tissue sections from 17 LMP tumors and 16 low- and 257 high-grade carcinomas.
2009-06-08 | E-GEOD-14001 | biostudies-arrayexpress