Ascites exosomal lncRNA PLADE enhances platinum sensitivity by inducing R-loop in ovarian cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE247337 | GEO | 2023/11/15
REPOSITORIES: GEO
Similar Datasets
Project description:Ascites exosomal lncRNA PLADE enhances platinum sensitivity by inducing R-loop in ovarian cancer
| PRJNA1037123 | ENA
Project description:Ovarian cancer is one of the leading causes of death in females in the world. High-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype, and the platinum-resistance is a clinical challenge. HGSOC frequently spreads to the peritoneal cavity and causes carcinomatous peritonitis. Extracellular vesicles (EVs) are lipid-bilayer nanoparticles containing various bioactive molecules. Thus, EVs mediate cell-to-cell communication and contribute to cancer progression. Moreover, EVs stably exist in the body fluid, including serum and ascites. This study investigated the ascites EV miRNA profiles of platinum-resistant and platinum-sensitive HGSOC.
2025-09-03 | GSE273636 | GEO
Project description:High-grade serous ovarian cancer (HGSOC) represents the most lethal type of gynecological cancer, with platinum resistance being a serious challenge in HGSOC treatment. Long non-coding RNA (lncRNA) plays critical regulatory roles in the occurrence and development of various cancers, including HGSOC. Here, using RNA sequencing of tumor exosomes from HGSOC patients, we identified lncRNA CATED was significantly upregulated in both tumors and tumor-derived exosomes in platinum-resistant HGSOC, and low CATED level correlated with good prognosis. Functionally, CATED enhanced cisplatin resistance via promoting cell proliferation and decreasing apoptosis both in vitro and in vivo. These effects could also be transferred via CATED-overexpressing exosomes from donor cells and tumor exosomes from HGSOC patients. Mechanistically, CATED bound to and upregulated DHX36 via PIAS1-mediated SUMOylation at K105 site, and elevated DHX36 increased the downstream RAP1A protein levels by enhancing RAP1A mRNA translation, consequently activating MAPK pathway to promote platinum resistance in HGSOC. ASO-mediated knockdown of CATED reversed the platinum resistance in exosome-transferring mouse models through DHX36-RAP1A-MAPK pathway. Overall, these findings offer new insights into the critical roles of exosomal lncRNAs in platinum resistance, and indicate that CATED may be a potential target of HGSOC treatment.
2025-09-03 | GSE282004 | GEO
Project description:Background: Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients. The objective of this study was to identify and validate novel epigenetic markers of chemoresponse using genome-wide analysis of DNA methylation in extreme chemoresponsive HGSOC patients. Methods: Genome-wide next-generation sequencing was performed on methylation-enriched tumor DNA of two HGSOC patient groups with residual disease, extreme responders (≥18 months progression-free survival (PFS), n = 8) and non-responders (≤6 months PFS, n = 10) to platinum-based chemotherapy. DNA methylation and expression data of the same patients were integrated to create a gene list. Genes were validated on an independent cohort of extreme responders (n = 21) and non-responders (n = 31) using pyrosequencing and qRT-PCR. In-silico validation was performed using publicly available DNA methylation (n = 91) and expression (n = 208) datasets of unselected advanced stage HGSOC patients. Functional validation of FZD10 on chemosensitivity was done in ovarian cancer cell lines using siRNA-mediated silencing. Results: Integrated genome-wide methylome and expression analysis identified 45 significantly differentially methylated and expressed genes between two chemoresponse groups. Four genes FZD10, FAM83A, MYO18B and MKX were successfully validated in an external set of extreme chemoresponsive HGSOC patients. High FZD10 and MKX methylation was related with extreme responders and high FAM83 and MYO18B methylation with extreme non-responders. In publicly available advanced stage HGSOC datasets, FZD10, MYO18B and MKX methylation levels were associated with PFS. High FZD10 methylation was strongly associated with improved PFS [HR=0.43, 95%CI=0.27-0.65, p=0.0002]. Consistently, low FZD10 expression was associated with improved PFS [HR=1.36, 95%CI=0.99-1.88, p=0.058]. FZD10 silencing caused significant sensitization towards cisplatin treatment in survival assays and apoptosis assays. Conclusions: By applying genome-wide integrated methylome analysis on extreme chemoresponsive HGSOC patients, we identified novel clinically relevant, epigenetically-regulated markers of platinum-sensitivity in HGSOC patients. The clinical potential of these markers in predictive and therapeutic approaches has to be further validated in prospective studies.
2017-08-17 | GSE97128 | GEO
Project description:Peritoneal carcinomatosis with malignant ascites is associated with dismal prognosis in gastric cancer. Malignant ascites is the most relevant body fluid in which to seek diagnostic biomarkers for peritoneal carcinomatosis. We aimed to identify and validate ascites-derived circulating microRNAs (miRNAs) that are differentially expressed between liver cirrhosis-associated benign ascites (LC-ascites) and gastric cancer-associated malignant ascites (GC-ascites). MiRNA expression levels were investigated in three independent cohorts. Overall, 165 ascites samples (73 LC-ascites and 92 GC-ascites) were obtained from the National Biobank of Korea. Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n = 22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were used to validate the expression levels of selected miRNAs in the training (n = 70) and validation (n= 73) cohorts. In addition, the levels of carcinoembryonic antigen (CEA), a commonly used tumor marker, were determined in the ascites samples. Expression levels of miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly lower in the GC-ascites samples than in the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC] = 0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved if CEA and miR-181b-5p were analyzed together (AUC = 0.981 and 0.946 for the training and validation cohorts, respectively). Overall, we identified ascites-derived circulating miRNAs capable of differentiating non-malignant ascites and GC-ascites, and demonstrated that the combined use of miR-181b-5p and CEA produces the optimal diagnostic yield.
2019-02-12 | GSE126399 | GEO
Project description:RNA-seq of FFPE-macrodissected HGSOC tissues and solid and ascites-derived HGSOC 2D cultures
| PRJEB40519 | ENA
Project description:Introduction: Although High Grade Serous Ovarian Cancer (HGSOC) is considered a chemo-responsive disease, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival of <6 months. Validated biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of resistance. Methods: Differential DNA methylation was investigated in independent tumour sets using Illumina 27K HumanMethylation arrays and validated by bisulphite pyrosequencing. Gene expression was by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction into ovarian cancer cell lines. Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in HGSOC which recur by 6 months compared to after 12 months and/or with RECIST response (p<0.05, q<0.05). A decrease in methylation at these intragenic CpG sites was significantly correlated with decreased MSX1 gene expression. Low expression of MSX1 was associated with poor progression-free survival independent of known clinical prognostic features (p=0.014). Three mutant or wild-type TP53 expressing ovarian cancer cell lines, resistant to cisplatin, have reduced MSX1 expression compared to matched parental, platinum sensitive, lines. Re-expression of MSX1 in resistant lines led to cisplatin sensitisation, increased apoptosis, increased p21 and BAX expression. However, in two TP53-null cell lines, MSX1 failed to change cisplatin sensitivity. Conclusion: Hypomethylation of MSX1 is a biomarker of resistant HGSOC disease at presentation and identifies a novel mechanism of platinum drug resistance. Bisulphite converted DNA from the 86 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2015-11-26 | E-GEOD-75414 | biostudies-arrayexpress
Project description:Differ from the aggressive nature of HGSOC (high grade serous ovarian cancer), LGSOC (low grade serous ovarian cancer) is characterized by an early age of disease onset, slow growth pattern, and poor response to chemotherapy. To understand more specifically the underlying gene profiling discrepancy that contributes to their behavior distinction, we performed parallel gene expression profiling in 9 magnetic sorted tumor cells samples from matched primary tumors, ascites and metastases of 3 LGSOC patients as in HGSOC. By comparing the expression data among primary tumor cells, ascitic tumor cells and metastasis tumor cells, we identified a set of differential expressed genes along LGSOC progression. Further study revealed that the gene phenotype perturbance along LGSOC progression was quite different from that of HGSOC patients. We used microarrays to profile the expression of 9 matched tumor cells samples in order to identify molecular alteration between primary tumor cells, ascitic tumor cells and metastatic tumor cells in low grade serous ovarian cancer.
2017-12-19 | GSE73091 | GEO
Project description:The purpose of our study was to explore the proteomic profile of ascites exosomes from Epithelial ovarian cancer (EOC) patients and to find potential prognosis markers for EOC.
2025-07-21 | PXD051234 | Pride
Project description:Ovarian cancer is characterized by transcoelomic metastasis into the peritoneal cavity. The peritoneal malignant ascites is enriched with ovarian cancer cells and a small amount of tumor-associated immune cells which create a unique microenvironment actively contributing to progression of the disease. However, it remains unclear how cancer cells communicate to its local environment under the influence of chemotherapy. To address this issue, we performed LC-MS/MS analyses of several primary cultures of ovarian cancer cells from chemonaive malignant ascites incubated for 3 days with autologous pre- or post-chemotherapy ascitic fluids. Enrichment analysis identified prominent upregulation of proteins associated with pathways of DNA repair and cell cycle regulation in tumor cells incubated with ascitic fluids after chemotherapy. Consistently with these data, ascites after therapy increased the resistance of ovarian cancer cells to cisplatin. These findings demonstrate that under stress condition cancer cells can secrete signaling molecules into the extracellular space and contribute to the emergence of tumor chemoresistance during short time period.
2024-05-29 | PXD045647 | Pride