Single cell RNA-seq analysis of ovarian cancer ascites
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE146026 | GEO | 2020/05/01
REPOSITORIES: GEO
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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:To understand the diversity of expression states in IDH-wildtype Glioblastomas, we profiled 24,131 single cells from 28 patients with GBM by single-cell RNA sequencing (7,930 cells by Smartseq2 and 16,201 by 10X).
2019-07-07 | GSE131928 | GEO
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 is remain 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 ovarian cancer ascites from the same patients before and after chemotherapy. We found that neoadjuvant chemotherapy causes a significant changes in the composition of ascites, and these changes are similar in samples obtained from all patients (n=10). Functional annotation of upregulated proteins with the use of KEGG and GO databases revealed that malignant ascites after chemotherapy were enriched with the cluster of spliceosomal proteins. These splicing factors were linked to induction of epithelial-to-mesenchymal transition leading to a more aggressive phenotype of cancer cells.
2024-05-29 | PXD019327 | Pride
Project description:Ovarian cancer patients are generally diagnosed at stage III/IV, when ascites is common. The volume of ascites positively correlates with the extent of metastasis and negatively with prognosis. Membrane GRP78, a stress-inducible endoplasmic reticulum chaperone which also appears on the plasma membrane (memGRP78) of aggressive cancers, plays a crucial role in the maintenance of embryonic stem cells. Our present study demonstrates that tumor cells isolated from ascites generated by epithelial ovarian cancer (ID8 cells) bearing mice have increased memGRP78 expression compared to ID8 cells in normal culture. We hypothesize that these ascites associated memGRP78+ cells are cancer stem-like cells (CSC) and memGRP78 is functionally important in CSCs. Supporting this hypothesis, we show that memGRP78+ cells isolated from ascites have increased sphere forming and tumor initiating abilities compared to memGRP78- cells. When the tumor microenvironment is recapitulated by adding ascites fluid to cell culture, ID8 cells express more memGRP78 and increased self-renewing ability compared to those cultured in medium alone. Moreover, compared to their counterparts cultured in normal medium, ID8 cells cultured in ascites, or isolated from ascites, show an increased expression of stem cell markers Sca-1, Snail and SOX9. Importantly, antibodies directed against the carboxy (COOH)-terminal domain of GRP78 significantly reduce the self-renewing ability of murine and human ovarian cancer cells pre-incubated with ascites, associated with a decreased phosphorylation of Akt and GSK3α, and reduced level of the transcriptional factor Snail. Based on this data, we suggest that memGRP78 is a logical therapeutic target for late stage ovarian cancer. Two types of ovarian cancer cells from different organ sites are profiled by gene expression. Parental cells (ID8) and ID8 cells which have metastasized to Ascites (AS).
2015-03-09 | E-GEOD-61285 | biostudies-arrayexpress
Project description:We present evidence for an autocrine cytokine network in human ovarian cancer that has paracrine actions on the tumour microenvironment. In experiments using bioinformatics analysis of large gene expression array datasets and ovarian cancer biopsies, we found that the inflammatory cytokines TNF-α and IL-6, the chemokine receptor CXCR4 and its ligand CXCL12, are co-regulated in malignant cells. We named this co-regulation the TNF network. We had access to a unique set of ascites cell samples from patients with advanced ovarian cancer treated with the therapeutic anti-human TNF-α antibody infliximab. Serial samples pre and during treatment were obtained during paracentesis (drainage of ascites fluid for symptomatic relief). In nine of these patients there was sufficient mRNA available for gene expression profile analysis before treatment. The Affymetrix GeneChip Human Genome U133Plus 2.0 arrays were used to define gene expression profiles in each of the ascites cell samples.
2009-12-31 | E-GEOD-18681 | biostudies-arrayexpress
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
Project description:We used scRNAseq approaches (Smartseq2 and 10X Genomics) to investigate the diversity of small intestinal stromal cells.
2022-05-31 | GSE154821 | GEO
Project description:Ascites is a valuable source of cancer biomarkers, because it contains a variety of secreted and shed proteins from cancerous cells. Conversely, most proteomic studies on ascites have focused on ovarian cancer and provided insufficient depth for biomarker discovery. Further, no proteomic analysis of ascites from gastric cancer has been reported. To this end, we profiled the human ascites proteome to obtain a pool of biomarker candidates using comprehensive proteomic strategies. Subsequently, label-free quantitation was performed to compare the abundance of proteins between benign disease and gastric cancer patients.
2018-04-16 | PXD004501 | Pride
Project description:Ovarian cancer (OC) ranks among the deadliest cancers in women. Lack of symptoms, rapid spread of metastases and common chemoresistance contribute to unfortunate fate of majority of OC patients, especially those having high-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of OC. Many HGSC patients have excess fluid in the peritoneum at the stage of diagnosis called ascites. Ascites is basically a tumor microenvironment (TME) in the liquid form containing various cells, proteins and also extracellular vesicles (EVs). EVs are small membrane-bound particles that convey proteins, lipids and nucleic acids between cells and their cargo reflects the cell of origin. EVs play important role in cancerogenesis and hold great promise as disease biomarkers as well as potential therapeutic targets. Small size and polydispersity of EVs bring various challenges to their isolation and characterization, including method-dependent enrichment of different EV subtypes as well as contaminants. We isolated EVs from ascites of 11 patients by two different methods (ultracentrifugation coupled to sucrose cushion and size-exclusion chromatography, qEV column) and analyzed them by mass spectrometry. We identified core ascitic EV proteins present in all patients that contain typical EV markers and are devoid of method-dependent contaminants. To cover interpatient heterogeneity, we expanded this “core proteome” with proteins found in majority of patients. Next, we compared them with proteins of EVs from related control fluids and uncovered proteins present only on EVs from HGSC patients. We believe this list of proteins contain both important players of HGSC progression as well as potential biomarkers. Using single cell RNA sequencing data, we mapped the origin of EVs to different types of cells present in malignant ascites. Our results suggest that EVs in ascites do not come predominantly from tumor cells, but rather from variety of non-malignant cell types including cancer-associated fibroblasts and tumor-associated macrophages, which presence in ascites was confirmed by flow cytometry. This emphasizes the recently appreciated role of TME in the progression of HGSC. To conclude, this is the first study attempting to link EV composition to the cell types producing it. As such it opens numerous avenues both for better understanding of EV role in tumor promotion/prevention and for the improved HGSC diagnostics.
2024-05-24 | PXD041751 | Pride
Project description:Background: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-M-NM-:B survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions. The expression profiles from human peritoneal mesothelial cells (HPMC) cultures exposed to peritoneal fluids and ovarian cancer ascites were compared using the Agilent Whole Human Genome Oligonucleotide microarrays, containing 44,000 genes. Microarrays were performed on HPMCs exposed to 3 malignant ascites from women with advanced (stage III/IV) serous OC and two benign peritoneal fluids. First, we generated lists of significantly up-regulated and down-regulated genes that were differentially expressed between OC ascites (OVC346, OVC508 and OVC509) and control OV370 peritoneal fluid. Then, the set of genes that were commonly expressed between control peritoneal fluids (OV370 and OV401) were subtracted from the first list of genes to generate a dataset of differentially expressed genes between malignant ascites and benign peritoneal fluids.
2014-04-14 | E-GEOD-55065 | biostudies-arrayexpress