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Ovarian Cancer Ascites Inhibits Transcriptional Activation of Natural Killer Cells partly through MUC16

ABSTRACT: Ovarian Cancer Ascites Inhibits Transcriptional Activation of Natural Killer Cells partly through MUC16

PROVIDER: PRJNA643790 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12136300.fastq.gz	Fastqsanger.gz
	SRR12136301.fastq.gz	Fastqsanger.gz
	SRR12136302.fastq.gz	Fastqsanger.gz
	SRR12136303.fastq.gz	Fastqsanger.gz
	SRR12136304.fastq.gz	Fastqsanger.gz

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Ovarian Cancer Ascites Inhibits Transcriptional Activation of Natural Killer Cells partly through MUC16

Project description:Purpose:To investigate the effect of ascites of ovary cancer on human NK cells at the genome-wide level.

2021-01-01 | GSE153713 | GEO

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2016-05-17 | E-GEOD-80063 | biostudies-arrayexpress

Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites

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.

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Ovarian Cancer Ascites Inhibits Transcriptional Activation of NK Cells Partly through CA125.

Project description:Malignant ascites is a common clinical problem in ovarian cancer. NK cells are present in the ascites, but their antitumor activity is inhibited. The underlying mechanisms of the inhibition have yet to be fully elucidated. Using an Fcγ receptor-mediated NK cell activation assay, we show that ascites from ovarian cancer patients potently inhibits NK cell activation. Part of the inhibitory activity is mediated by CA125, a mucin 16 fragment shed from ovarian cancer tumors. Moreover, transcriptional analyses by RNA sequencing reveal upregulation of genes involved in multiple metabolic pathways but downregulation of genes involved in cytotoxicity and signaling pathways in NK cells purified from ovarian cancer patient ascites. Transcription of genes involved in cytotoxicity pathways are also downregulated in NK cells from healthy donors after in vitro treatment with ascites or with a CA125-enriched protein fraction. These results show that ascites and CA125 inhibit antitumor activity of NK cells at transcriptional levels by suppressing expression of genes involved in NK cell activation and cytotoxicity. Our findings shed light on the molecular mechanisms by which ascites inhibits the activity of NK cells and suggest possible approaches to reactivate NK cells for ovarian cancer immunotherapy.

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Project description:Comparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.

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Expression data of ascites treated peritoneal carcinomatosis human cell lines

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Genome-wide analysis of mRNA expression alterations in Stage III-IV high-grade serous ovarian cancer patients exhibiting clinically defined differences in ascites volume (high volume ascites versus low volume ascites)

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