Serum miRNA as Potential Biomarkers for ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201712 | GEO | 2023/04/27
REPOSITORIES: GEO
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Project description:Ovarian cancer (OC) is the one of the most common gynecological tumors with high morbidity and mortality. Alterations in serum N-glycosylation have been observed in many diseases, and specific N-glycans of serum could be used for disease diagnosis or prognosis. However, the association between serum N-glycome profiles and OC progression remains unclear. Herein, high-throughput mass spectrometry was applied to characterize serum N-glycome profile in individuals with healthy controls, benign neoplasm and different stages of OC patients. It was observed that high-mannosylation, neutral bisection and agalactosylation of serum glycoproteins were uniformly increased in the initiation and development of OC, but sialylation was substantially changed on an opposite trend. Additionally, agalactosylation, high-mannosylation and sialylation gained at least moderately accurate merit for diagnosis of both OC and benign neoplasm. Notably, serum N-glycome profile could accurately discriminate OC patients from benign cohorts, with a comparable or even higher diagnostic score compared with CA125 and HE4. Furthermore, bioinformatics verified the differential expression of glycogens in OC progression. Significantly, strong correlations were found between CA 125 and high-mannosylation, galactosylation and sialylation. These findings demonstrated the great potential of serum N-glycome for OC diagnosis and precancerous lesion prediction, paving a new way for OC screening and monitoring.
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Project description:Ovarian cancer is a major cause of cancer mortality among women largely due to late diagnosis of advanced stage metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins particularly associated with metastatic disease so that we can better understand the metastatic process and identify potential therapeutic targets. Proteins are the target of many recently developed cancer treatments, but an often neglected aspect of biomarker discovery is protein glycosylation, especially those involving tumor-associated carbohydrate antigens (TACAs) such as sialyl-Lewis(x) (SLe(x) and sialyl-Lewis(a) (SLe(a), which have been identified in various cancers. Although it is already known that considerable changes in protein glycosylation are major contributors to the initiation, progression and metastasis of tumors, specifics about glycosylation changes particularly important to the metastatic process are still lacking. In this report we describe the results of a combined glycomic and proteomic study of metastatic ovarian cancer (OC) ascites fluids. Glycoproteins in ascites fluid were enriched by affinity binding to lectins (ConA or WGA) and other affinity matrices. Separate glycomic and proteomic analyses were performed as well as glycopeptide analyses. Relative abundances of different N-glycan groups and proteins were identified from original ascites fluids and corresponding lectin bound samples. Levels of biomarkers CA125, MUC1 and fibronectin were also monitored in these samples by Western blot analysis. N-glycan analysis of ascites fluids showed the presence of large, highly fucosylated and sialylated, complex and hybrid glycans, some of which were not observed in normal serum. Proteins in OC ascites that were more abundant or not present in the serum control, were haptoglobin, fibronectin, lumican, fibulin, hemopexin, ceruloplasmin, alpha-1-antitrypsin and alpha-1-antichymotrypsin. Glycopeptide analysis identified N- and O-glycans in clusterin, hemopexin, and fibulin that were present in OC ascites.
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Project description:To validate prediction marker of ovarian cancer patients, comprehensive analysis of serum microRNA of ovarian cancer patients were performed.
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Project description:Peritoneal dissemination of ovarian cancer (OC) correlates with poor prognosis, but the mechanisms underlying the escape of OC cells from the intraperitoneal immune system have remained unknown. We here identify pigment epithelium–derived factor (PEDF) as a regulator of OC cell dissemination, which functions through induction of CD206+ IL-10–producing macrophages. High PEDF gene expression was associated with poor prognosis in OC patients. Concentrations of PEDF in ascites and serum were significantly higher in OC patients than those with more benign tumors and correlated with early recurrence of OC patients, suggesting that PEDF might serve as a prognostic biomarker. Bromodomain and extraterminal (BET) inhibitors were found to reduce PEDF expression and limit both OC cell survival and CD206+ macrophage induction in the peritoneal cavity. Our results thus implicate PEDF as a driver of OC dissemination and identify a BET protein–PEDF–IL-10 axis as a promising therapeutic target for OC.
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Project description:Global microRNA expression profiling of serum were collected using Agilent miRNA microarrays (G4471A Human, Amadid 29297, Sanger 14) carrying 887 individual human miRNA probes. Two different sources of RNA were analyzed: serum from healthy controls (N=5) and patients with ovarian carcinoma (CA, n=5)
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Project description:Epithelial ovarian cancer (EOC) is the type of ovarian cancer having the highest mortality rate. Because of the asymptomatic characteristic and a few diagnostic tests, it is mostly diagnosed at advanced stages. Therefore, this study aims to gain the predictive and/or early diagnostic novel circulating miRNAs for EOC. Firstly, microarray analysis of miRNA expression level is performed on plasma samples from pathologically confirmed EOC patients and matching healthy individuals; EOC tissue samples and benign ovarian neoplastic tissues. 31 significantly dysregulated miRNAs in serum and 3 miRNAs in tissue were identified by microarray. The results were validated using RT-qPCR. KEGG database was used for the target gene and pathway analysis. Three miRNA from EOC serum (hsa-miR-1909-5p, hsa-miR-885-5p, hsa-let-7d-3p) and one microRNA from tissue samples (hsa-miR-200c-3p) were validated as significant enough to distinguish EOC patients from healthy individuals. KEGG pathway enrichment analysis showed 7 significant pathways, which are prion diseases, proteoglycans in cancer, oxytocin signaling pathway, hippo signaling pathway, adrenergic signaling in cardiomyocytes, oocyte meiosis, and thyroid hormone signaling pathway, in which our validated miRNAs have a role. It supports our hypothesis that several miRNAs, in our case validated 4 miRNAs, can have the potential to be a biomarker of EOC diagnosis and treatment.
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Project description:Global microRNA expression profiling of serum were collected using Agilent miRNA microarrays (G4471A Human, Amadid 29297, Sanger 14) carrying 887 individual human miRNA probes. Two different sources of RNA were analyzed: serum from healthy controls (N=5) and patients with ovarian carcinoma (CA, n=5) Two conditions (CA, N), each condition is represented by 5 biological replicates
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Project description:High-grade serous ovarian cancer (HGSOC) represents the major histological type of ovarian cancer (OC), and lack of effective screening tools and early detection methods significantly contributes to the poor prognosis of HGSOC. Currently, there is no reliable diagnostic biomarkers for HGSOC. In this study, we performed liquid chromatography data-independent acquisition tandem-mass spectrometry on depleted serum samples from 26 HGSOC cases and 24 healthy controls (HCs) to discover potential HGSOC diagnostic biomarkers. A total of 1,847 proteins were identified across all samples, among which 116 proteins showed differential expressions between HGSOC patients and HCs. Network modeling showed activations of coagulation and complement cascades, platelet activation and aggregation, NET formation, TLR4, IGF, and TGF-β signaling, and suppression of lipoprotein assembly and FcγR activation in HGSOC. Based on the network model, we prioritized 28 biomarker candidates, and validated 18 of them using targeted MS assays in an independent cohort. Predictive modeling showed a sensitivity of 1 and specificity of 0.91 in the validation cohort. Finally, in vitro functional assays on four potential biomarkers (FGA, VWF, ARHGDIB, and SERPINF2) suggested that they may play an important role in cancer cell proliferation and migration in HGSOC.
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Project description:MicroRNA miRNA expression profiles for human ovarian carcinomas were examined to investigate the miRNA involvement in the development of this neoplasia. miRNA microarray analysis identified statistical unique profiles, which could discriminate ovarian carcinomas from noncancerous ovarian tissues, and different groups of tumors classified according to histo-pathological characteristics.
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