Project description:A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9-10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.
Project description:Background: Tumor microenvironment is well known to have a key role in tumor development. Extracellular vesicles are capable in cell signaling transduction and important in regulation of tumor microenvironment. Objective: To investigate whether peritoneal fluid–derived extracellular vesicles help regulate the tumor microenvironment in the malignant transformation of endometriosis. Methods: Samples of peritoneal fluid were taken from women with benign gynecological disease, endometriosis, or endometriosis-associated ovarian cancer. Small extracellular vesicles in the samples were isolated via ultracentrifugation and characterized by western blotting, transmission electron microscopy, and nanoparticle tracking. A global microRNA (miRNA) expression profile array was used to analyze miRNA abundance in peritoneal fluid–derived small extracellular vesicles. Candidate miRNAs were quantified by reverse transcription PCR to assess their potential role in cell migration. Results: A total of 22 miRNAs were identified from the analysis of miRNAs in peritoneal fluid–derived small extracellular vesicles from patients with endometriosis or endometriosis-associated ovarian cancer. We confirmed that each miRNA was expressed in various ovarian cell lines. The miRNA miR-302f was consistently highly expressed in both clinical specimens and ovarian cell lines from patients with endometriosis, yet expression was relatively low in specimens and cell lines from patients with endometriosis-associated ovarian cancer. A bio-functional assay revealed that miR-302f regulates cell migration. Finally, the possible target mRNAs of miR-302f were identified in the Gene Expression Omnibus database. Conclusions: These data may provide a basis for the development of novel therapeutic strategies for endometriosis-associated ovarian cancer patients by downregulating PDGFRA abundance in cancer cells via overexpression of miR-302f.
Project description:No residual disease after debulking Surgery (R0 resection) is the most critical independent prognostic factor for advanced ovarian cancer (AOC). Therefore, it is of paramount importance to preoperative estimate the likelihood of R0 resection for choosing the best therapeutic strategy. Our study aimed to develop a non-invasive and reliable detection method for AOC patients with a high risk of residual disease. An integrated plasma small extracellular vesicles (sEVs) microRNA profiling was generated by RNA sequencing in AOC patients with no residual disease patients (R0) and residual disease(non-R0). We identified and validated a logistic model based on plasma sEVs miRNAs to predict residual disease in AOC patients.
Project description:No residual disease after debulking Surgery (R0 resection) is the most critical independent prognostic factor for advanced ovarian cancer (AOC). Therefore, it is of paramount importance to preoperatively estimate the likelihood of R0 resection for choosing the best therapeutic strategy. Our study aimed to develop a non-invasive and reliable detection method for AOC patients with a high risk of residual disease. An integrated plasma small extracellular vesicles (sEVs) microRNA profiling was generated by RNA sequencing in AOC patients with no residual disease patients (R0) and residual disease (non-R0). We identified and validated a logistic model based on plasma sEVs miRNAs to predict residual disease in AOC patients.
Project description:Comparison of various ovarian tumors and ovarian cell lines. Keywords: Various ovarian tumors and cell lines. Samples from ovarian tumors and ovarian cell lines were examined for their microRNA expression patterns.