Single-cell RNA-seq profiling of treatment-naïve chemo-refractory and chemo-sensitive ovarian cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1282622 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This dataset contains single-cell RNA-seq data from treatment-naïve biopsies of nine patients diagnosed with ovarian high-grade serous carcinoma (HGSC), including four chemo-refractory and five chemo-sensitive cancers. Four of the samples (EOC204, EOC115, EOC649, EOC1127) are newly generated, while five samples have been previously published (GSE165897). The data was generated as part of the DECIDER observational trial (NCT04846933) to investigate the molecular drivers of chemo-refractory HGSC. Key findings from the study indicate that chemo-refractory HGSC is associated with reduced interferon type I (IFN-I) activity and enhanced hypoxia pathway activity, while baseline IFN-I pathway activity in chemo-naïve cancer serves as an independent prognostic factor for chemotherapy response.
2025-07-03 | GSE300897 | GEO
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:A considerable subset of gynecologic cancer patients’ experiences disease recurrence or acquired resistance, which contributes to high mortality rates in ovarian cancer (OC). Our prior studies showed that quinacrine (QC), an antimalarial drug, enhanced chemotherapy sensitivity in treatment-refractory OC cells, including artificially generated chemoresistant and high-grade serous OC cells. In this study, we investigated QC-induced transcriptomic changes to uncover its cytotoxic mechanisms of action. Isogenic pairs of OC cells generated to be chemo-resistant and chemo-sensitive counterparts were treated with QC followed by RNAseq analysis. Validation of selected expression results and database comparison analyses indicated the ribosomal biogenesis (RBG) pathway is inhibited by QC. RBG is commonly upregulated in cancer cells and is emerging as a drug target. We found that QC attenuates the in vitro and in in vivo expression of nucleostemin (NS/GNL3), a nucleolar RBG and DNA repair protein, and the RPA194 catalytic subunit of Pol I that results in RBG inhibition and nucleolar stress. QC promotes the redistribution of fibrillarin in form of extranuclear foci and nucleolar caps, an indicator of nucleolar stress conditions. In addition, we found that QC-induced downregulation of NS disrupted homologous recombination repair both by reducing NS protein levels and parylation resulting in reduced RAD51 recruitment to DNA damage. Our data suggests that QC inhibits RBG and this inhibition promotes DNA damage by directly downregulating the NS-RAD51 interaction. Additionally, QC showed strong synergy with PARP inhibitors in OC cells. Overall, we found that QC by downregulates the RBG pathway, induces nucleolar stress, supports the increase of DNA damage, and sensitized cells to PARP inhibition, which supports new therapeutic stratagems for treatment-refractory OC. Our work offers support for targeting RBG in OC and determines NS to be a novel target for QC.
2021-09-29 | GSE176246 | GEO
Project description:Seven pairs of hormone sensitive and hormone refractory prostate cancer xenografts
2007-12-12 | E-GEOD-847 | biostudies-arrayexpress
Project description:We profile expression in serous epithelial ovarian carcinomas to assess the possibility of an miRNA signature associated with chemoresistance. Resistance to the available therapies is one of the main causes of low survival of patients with advanced epithelial ovarian cancer, thus representing an emergency in oncology. Here, we profiled miRNA expression in 86 naïve serous epithelial ovarian carcinomas (EOCs) to assess the possibility of miRNAs associated with chemoresistance. We identified 23 miRNAs associated with chemoresistance, of which three (miR-484, miR-642 and miR-217) were confirmed in the validation set (112 independent patients). The study of miR-484 role demonstrated that it regulated the chemoresistance of EOC cells acting not on cancer cells but on tumor vasculature. In particular, miR-484 is produced and secreted by chemosensitive EOC, therefore regulating the production of VEGFB by cancer cells and the expression of VEGFR2 in endothelial cells. Overall, we demonstrated that a three-miR signature can classify the response to chemotherapy and that chemoresistance in EOC relays, at least in part, on the control of tumor angiogenesis, indicating new options in the treatment of these patients. We analyzed tumor samples (<5% of normal tissue) from FFPE blocks of 86 patients with serous ovarian carcinomas.
2013-05-17 | E-GEOD-43867 | biostudies-arrayexpress
Project description:RNA-Seq of pre-chemo high-grade serous ovarian tumors
| PRJNA671754 | ENA
Project description:Quinacrine induces nucleolar stress in treatment-refractory ovarian cancer
| PRJNA735553 | ENA
Project description:We profile expression in serous epithelial ovarian carcinomas to assess the possibility of an miRNA signature associated with chemoresistance. Resistance to the available therapies is one of the main causes of low survival of patients with advanced epithelial ovarian cancer, thus representing an emergency in oncology. Here, we profiled miRNA expression in 86 naïve serous epithelial ovarian carcinomas (EOCs) to assess the possibility of miRNAs associated with chemoresistance. We identified 23 miRNAs associated with chemoresistance, of which three (miR-484, miR-642 and miR-217) were confirmed in the validation set (112 independent patients). The study of miR-484 role demonstrated that it regulated the chemoresistance of EOC cells acting not on cancer cells but on tumor vasculature. In particular, miR-484 is produced and secreted by chemosensitive EOC, therefore regulating the production of VEGFB by cancer cells and the expression of VEGFR2 in endothelial cells. Overall, we demonstrated that a three-miR signature can classify the response to chemotherapy and that chemoresistance in EOC relays, at least in part, on the control of tumor angiogenesis, indicating new options in the treatment of these patients.
2013-05-17 | GSE43867 | GEO
Project description:Background: High-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological malignancy, exhibiting marked heterogeneity that complicates treatment. The implications of intratumoral androgen metabolism and signalling, particularly involving 11-oxygenated androgens, in HGSOC remains poorly understood. Methods: We analysed expression of key androgen-metabolizing enzymes and androgen receptor (AR) in relation to tumor site, chemotherapy response, and survival using two public HGSOC cohorts. Quantitative gene expression and steroid metabolism assays upon incubation with classic and 11-oxyandrogen precursors were performed in six HGSOC cell lines and one normal ovarian epithelial line. Untargeted transcriptomic and metabolomic profiling were performed to assess cellular responses to potent classic and 11-oxygenated androgens in the AR-positive OVSAHO cell line. Results: Differential expression of steroid-metabolizing enzymes and AR were observed between primary and metastatic tumors and chemo-sensitive and chemo-resistant tumors. Higher intra-tumoral expression of HSD11B2, HSD17B2, and AR correlated with improved survival, whereas elevated PAPSS1/2 and HSD17B4 predicted poorer outcomes. In vitro, classic androgen precursors showed limited conversion to bioactive androgens and did not generate 11-oxyandrogens. In contrast, 11-oxyandrogen precursors were efficiently converted to the potent AR agonist 11KT in chemo-sensitive HGSOC cell lines, but not in chemo-refractory or control lines. Potent classic and 11-oxyandrogens induced stress-adaptive and proliferative transcriptional responses and reduced intracellular amino acid content. These changes were associated with a trend toward reduced cell proliferation. Conclusions: Our findings offer mechanistic insight into local androgen and 11-oxyandrogen metabolism and signalling in HGSOC and reveal steroid-induced cellular vulnerabilities that may synergize with chemotherapy or molecularly targeted therapies. These results further support the therapeutic potential of modulating steroid pathways in HGSOC.
2025-07-17 | GSE302881 | GEO
Project description:We performed RNA sequencing on 10 bulk pre-chemo tumor samples collected from 5 patients with HGSOC.
2020-12-14 | GSE160085 | GEO