Identification of differential expression miRNAs profile in serum samples of high-grade serous ovarian patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE235525 | GEO | 2023/10/29
REPOSITORIES: GEO
Similar Datasets
Project description:High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve the cure rate of HGSOC. Liquid biopsies are now becoming a new paradigm to develop novel biomarkers with diagnostic and prognostic purposes. The focus of this study was to detect the levels of circulating miRNAs in tissues and sera from patients with HGSOC and to evaluate their diagnostic value. To this end, an array-based discovery platform, followed by an innovative statistical approach of data normalization, was exploited, to identify miRNA species selectively expressed in serum of patients with HGSOC. Sera from 106 high grade serous ovarian carcinoma (HGSOC) and 24 healthy controls were used for profiling serum microRNA using a modified version of a commercially available microarray, with the aim of identifying differentially expressed microRNA between tumor patients and healthy controls.
2017-01-30 | E-MTAB-4667 | biostudies-arrayexpress
Project description:We measured gene expression in single-cell RNA sequencing samples from patients with high-grade serous ovarian cancer (HGSOC), for a study on improving HGSOC subtype definition by taking into account varying cell type proportions within tumors.
2020-10-03 | GSE158937 | GEO
Project description:Despite the similar histologic appearances of high-grade serous ovarian cancers (HGSOCs), clinical observations point to marked differences in their gross appearances. Some patients have numerous small nodules, whereas others have bulkier disease; some patients have widespread disease, whereas others have more localized disease. However, a systematic framework for classifying such gross morphologic differences does not exist. The implementation of a laparoscopic triage algorithm for patients with advanced HGSOC enabled us to prospectively obtain detailed video images of HGSOC that could be analyzed to identify morphologic subtypes. In this study, we aimed to develop and characterize a gross morphologic classification system for HGSOC. Specifically, we assessed whether HGSOC can be reliably divided into distinct gross morphologic subtypes and whether such subtypes have different clinical outcomes and molecular features.
2023-01-27 | PXD031518 | Pride
Project description:Ovarian cancer is one of the most common gynecologic malignancies globally, which is a significant cause of morbidity and mortality, accounting for 207,252 new deaths each year. The 5-year survival rate of this cancer is reported to be 26-42% and is often diagnosed in an advanced stage. Epithelial ovarian cancer (EOC) is a heterogeneous disease that comprises various histological subtypes. Of them, high-grade serous ovarian cancer (HGSOC) is the most common cancer subtype (70-80%), which is highly aggressive and grows rapidly. Despite the initial success observed with cytoreductive surgery and platinum-based chemotherapy, over 75% of HGSOC patients experience relapse following completion of first-line therapy. The challenge of tailoring therapeutic interventions to control progressive disease is compounded by the inherent cellular heterogeneity and genomic instability characteristic of HGSOC. While platinum chemotherapy remains the cornerstone of contemporary treatment, the grim reality persists that a majority of EOC patients develop chemotherapy resistance, resulting in a five-year survival rate of less than 50%. Numerous ovarian cancer studies have underscored the prognostic significance of factors such as age at diagnosis, disease stage, grade, histology, residual disease post-surgery, and disease recurrence. The genetic predisposition towards EOC indicates that high-grade HGSC exhibits significant chromosomal instability and carries mutations in the tumor protein 53 (TP53) gene, as well as mutations in the breast cancer genes BRCA1/2. Molecular markers like BRCA1/2 mutations and homologous repair deficiency in HGSOC have been validated as predictive of response to platinum therapy and poly-ADP polymerase (PARP) inhibitors. Furthermore, recent research has shed light on the prognostic potential of immune cell populations infiltrating ovarian tumor tissue. The Cancer Genome Atlas (TCGA) and other genomic studies of HGSOC have conducted extensive genomic and transcriptomic analyses of HGSOC to delineate its genomic landscape and facilitate the development of targeted therapies for this highly lethal malignancy. Key findings from previous studies include the prevalent mutation of TP53 genes, frequent and widespread DNA copy number alterations, identification of transcriptional signatures associated with clinical outcome and molecular subtype, and diverse mechanisms of BRCA1/2 inactivation. However, most studies have focused on HGSOC of white populations, and there is limited comprehensive molecular characterization of East Asian HGSOC, including those from Korea. In this study, we aimed to discern clinical and molecular factors distinguishing 123 HGSOC patients from the Korean population through an integrated analysis of clinical features, germline variants, somatic genomic alterations, and the tumor immune microenvironment.
2024-06-01 | GSE268514 | GEO
Project description:The genome-wide profiling of 5-hydroxymethylcytosine (5hmC) on circulating cell-free DNA (cfDNA) has revealed promising biomarkers for a variety of diseases. The purpose of our study is to investigate if 5hmC profiles from serum cfDNA are novel predictive biomarkers for the development of chemoresistance in high-grade serous ovarian cancer (HGSOC). We hypothesized that 5-hmC profiles associate with the development of chemoresistance and elucidate pathways that may drive chemoresistance in HGSOC. We developed a novel multivariate model based on clinico-pathologic data and a cfDNA-derived 5hmC-annotated gene that can predict response to platinum-based chemotherapy in intermediate-sensitive HGSOC. These results merit further investigation of our model as a predictive model.
2024-01-25 | GSE240535 | GEO
Project description:As the most fatal type of gynecological cancers, high-grade serous ovarian cancer (HGSOC) exhibits heterogeneity that obstacles therapeutics. Up to date, the pathogenesis of HGSOC remains poorly understood. Here, we performed the deep single-cell RNA sequencing (scRNA-seq) using 59,324 cells isolated from seven treatment-naïve HGSOC patients at early or late tumor stages and five age-matched non-malignant ovarian samples. Our sequencing data showed a highly complex ecosystem of tumor, immune and stromal cells based on their marker genes and functional properties. We showed that normal ovary-specific fibroblasts were carried with the properties of mesenchymal stem cells (MSCs), which could be reprogrammed to cancer-associated fibroblasts. During tumor progression, matrix CAFs (mCAFs) could induce the EMT properties of the tumor cells. Furthermore, the analysis of the early stage tumors illuminated enrichments of IDO-expressing macrophages, CD8+ TRM cells, and the activated CD8+ TEX cells (TRM-CXCL13), whereas those tumors at the late stages loss these features and expressed signatures related to epithelial-to-mesenchymal transition (EMT) program. Also, we characterized a specific chemokine-receptor communication in HGSOC tumor microenvironment, which may contribute to shape the HGSOC features. Our compendia of scRNA-seq results provide valuable insights for understanding the landscape of HGSOC ecosystem, which will be helpful in advancing HGSOC cancer diagnosis and therapy and enabling personalized approaches to the treatment.
2022-06-10 | GSE184880 | GEO
Project description:We aimed to discover and validate a panel of serum biomarkers for high grade serous ovarian cancer (HGSOC) using our lectin-magnetic bead array-coupled proteomics platform. Serum from age-matched women with HGSOC, benign tumours or healthy controls were analysed in discovery (UKCTOCS, n=30 and UKOPS, n=30) and validation (Australian Ovarian Cancer Study, n=95) cohorts using shotgun and targeted proteomics, respectively. A 7-lectin discovery screen shortlisted 60 candidate proteins and 3 lectins for validation, which revealed elevated levels of AAL, SNA or STL-binding FIBB, CO9, ITIH3, HPT, A1AT, AACT in HGSOC, while IBP3, A2MG, PON1, CHLE and ALS were reduced. Multimarker panels were developed using generalized regression with lasso estimation and leave-one-out cross-validation. The best performing panel comprised of 13 peptides from Solanum Tuberosum lectin (STL)-binding proteins with 96.3% area under the receiver operating curve, 97.7% specificity and 78.6% sensitivity for distinguishing HGSOC from benign and healthy groups. The peptides robust in cross-validations were from IBP3, KNG1, CO9, THRB, HPTR, HPT, FINC, FA10, GELS. The validated serum biomarkers show promise for early detection of HGSOC and should be further evaluated.
2023-10-24 | PXD032299 | Pride
Project description:Introduction/ Background: The epigenome represents and adds another facet of complexity to cancer that needs to be understood to categorize patients into those at risk of disease, recurrence, or treatment failure. Our goal is to compare DNA methylation status between controls vs HGSOC, and relate it with clinical outcomes. Methodology: A retrospective review of our institution’s advanced/ recurrent HGSOC patients yielded 99 cases with good quality DNA and RNA. 12 normal fallopian tubes were also collected and used as controls. Infinium Illumina methylationEPIC was used to characterize DNA methylation status and RNA seq to evaluate gene expression. T- tests were used to compare methylation patterns between controls vs HGSOC, primary vs recurrent, and optimal vs suboptimal surgical outcomes. Spearman’s rank correlation was used to evaluate association between degree of methylation and expression of identified genes. Validation of our findings used the cancer genome atlas (TCGA) database followed by C-statistics to assess degree of agreement. Results: Out of 66,069 methylation probes that interrogate known genes, 5,852 probes were significantly different between normal and HGSOC. This includes genes that are enriched in several pathways such as the RAS signaling pathway. A similar analysis of the TCGA database showed 2,075 differentially methylated probes. 1,891 probes were significant in both datasets giving a 70.1% degree of agreement. When comparing differential DNA methylation between primary and recurrent disease, there were 57 probes which represent 17 genes that were significantly different. When comparing optimal vs suboptimal surgical outcomes, 99 probes were significantly different wherein 29 genes show expected inverse correlation between methylation status and gene expression. Conclusions: There are significant differences in methylation patterns between HGSOC and fallopian tubes, primary vs recurrent tissues, and optimal vs sub-optimal surgical outcomes. Cataloging these phenomena in a well characterized clinical population will aid in determining groupings for precision medicine treatment cohorts in the future.
2019-07-01 | GSE133556 | GEO
Project description:Tumor infiltrating lymphocytes (TILs) play a significant role in the tumor microenvironment in high-grade serous ovarian cancer (HGSOC). To better understand the interactions and functions of TILs in HGSOC progression, we performed proteogenomic profiling of TILs in 65 tumors collected from 12 HGSOC patients.
2024-03-15 | PXD045710 | Pride
Project description:High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers for women, with a low survival rate, no early markers, a high rate of recurrence, and few therapeutic options. Forskolin, an activator of cyclic AMP signaling, has several anticancer activities, including against HGSOC, but has limited use in vivo. Its water-soluble derivative, colforsin daropate, has the same mechanism of action as forskolin and is used to treat acute heart failure. Here, we investigated the potential of colforsin daropate as a treatment for HGSOC. We found that colforsin daropate induced cell cycle arrest and apoptosis in cultured HGSOC cells and spheroids, but not in normal fallopian tube secretory cells and ovarian surface epithelial cells. Colforsin daropate also prevented HGSOC cells from invading ovarian surface cell layers in culture. In vivo, colforsin daropate reduced tumor growth, synergized with cisplatin (a standard chemotherapy in ovarian cancer care), and improved host survival in a subcutaneous xenograft model. These anti-tumor effects of colforsin daropate were mediated in part by its reduction in the abundance and transcriptional activity of the oncoprotein c-MYC, which is often increased in HGSOC. Our findings demonstrate that colforsin daropate may be a promising therapeutic that could be combined with conventional therapies to treat HGSOC.
2024-11-19 | GSE280516 | GEO