Genome-wide DNA methylome analysis identifies putative biomarkers associated with the survival of human ovarian cancers [30 cases]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168921 | GEO | 2021/08/11
REPOSITORIES: GEO
Similar Datasets
Project description:We conducted an epigenome-wide association study (EWAS) to evaluate global DNA methylation in EOC. In a retrospective cohort of 80 primary ovarian cancers, we observed that global DNA hypermethylation was significantly associated with high-grade tumors, platinum-resistance and poor prognosis. We determined that 8,600 differentially methylated probes (DMPs) were enriched in the intergenic regions of 4,673 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways.
2021-08-11 | GSE168926 | GEO
Project description:Stratification of a retrospective cohort of HGSOC based on its tissues of origin.
2020-09-29 | E-MTAB-9605 | biostudies-arrayexpress
Project description:Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC. We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validationsets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients. Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis. We designed a multi-stage, retrospective, nested case-control study to determine whether serum miRNA profiles can be used to predict EOC development. All samples were grouped into screening, training, and validation sets. A total of 560 plasma samples (360 cases and 200 controls) were obtained from Tianjin Medical University Cancer Institute and Hospital (TCIH) and Cancer Center of Nanjing Medical University. The cases and controls were well matched for age. The International Federation of Gynaecology and Obstetrics (FIGO) staging system was used to stage cases. All patients and controls were genetically unrelated, ethnic Han Chinese women who were permanent residents of the urban area of Tianjin and Nanjing. Controls with cardiovascular, respiratory, digestive, urinary, reproductive, and endocrine diseases were excluded. The study protocols were approved by the Tianjin and Nanjing Center review committees. In screening set, to detect generalizable miRNA signatures, we pooled serum samples of 10 early-stage cases (stage I), 10 late-stage cases (stage IIIc-IV), and 10 healthy controls, respectively, and analyzed these three pool samples using a TaqMan low-density array (TLDA set 2.0, Applied Biosystems) chip screening in the discovery stage. In training set, the miRNAs identified in the screening set were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on individual plasma samples of 76 EOC patients and 30 normal controls. In validation set, the validation set comprised a two-phase process. Promising associations from the screening and training set were evaluated in the validation phase I set, comprising 134 cases and 70 controls from Tianjin Center. The validation phase II set included samples of 77 EOC cases and 50 normal controls were from Tianjin Center and 73 EOC cases and 50 normal controls were from Nanjing Center.
2013-08-30 | E-GEOD-50472 | biostudies-arrayexpress
Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecological tumor in developed countries and is characterized by high biological and molecular heterogeneity. High-grade serous ovarian carcinoma (HGSOC) is the most frequent and intractable form of the disease, mainly due to its rapid dissemination into the abdominal cavity, a process that is tightly linked to peritoneal ascites. Despite several studies provided insights into the genetic and epigenetic alterations relevant in EOC, the precise molecular alterations involved in tumor onset and progression remain largely unknown. Here we provide an experimental framework to perform a comprehensive investigation of molecular alterations relevant in HGSOC and ovarian cancer stem cells (OCSC) biology. We relied on a well characterized experimental set derived from human HGSOC-associated ascites and consisting of primary tumor cells, OCSC-enriched spheroids and serially propagated patient-derived xenografts, in order to define genetic and transcriptional signatures associated to specific HGSOC evolutionary trajectories. Such signatures exhibited prognostic value in a large cohort of HGSOC patients and allowed to define PI3K signaling as a novel vulnerability in OCSCs. Thus, our approach proved effective for the identification of druggable targets in HGSOC ascites, which is a major player in relapse and poor prognosis.
2022-02-18 | GSE154950 | GEO
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:Environmental temperature directly affects the concentration of chemicals in the gas phase. Therefore, if the olfactory system does not adapt to environmental conditions may provide inadequate information about distance to or direction of odor sources. Previous reports in Drosophila melanogaster show that temperature induces changes in olfactory sensitivity in complete individuals. Electrophysiological analysis demonstrates that these changes initiate at the olfactory receptor organs. In this experiment we try to identify particular genes responsible for olfactory adaptation to increasing temperatures using receptor organs of Drosophila after exposure to high temperatures. With this aim, wild-type Canton-S flies were subjected to 48-hour treatments at 30 degrees C. We use a direct approach selecting the specific tissue and making 'a priori' the gene election for the microarray analysis. Differential gene-expression analyses at the third antennal segments are performed comparing control and treated flies.
2013-08-01 | E-MTAB-1228 | biostudies-arrayexpress
Project description:Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC. We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validationsets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients. Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.
2013-08-30 | GSE50472 | GEO
Project description:DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on bronchoalveolar lavage (BAL) cells. Bronchoscopies were performed in 18 COPD subjects and 15 controls (ex- and current smokers). DNA methylation was measured with Illumina MethylationEPIC BeadChip covering >850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology; 2) accelerated aging using Horvath’s epigenetic clock; 3) correlation with gene expression; and 4) colocalization with genetic variation. We found 1,155 Bonferroni significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age, but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were co-localized with COPD-associated SNPs. To the best of our knowledge, this is the first EWAS of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly impact expression. Almost half of DMPs were co-located with SNPs identified in previous GWAS of COPD, suggesting joint genetic and epigenetic pathways related to disease.
2022-03-17 | GSE198870 | GEO
Project description:Epithelial ovarian cancer (EOC) is the most serious of all gynecological cancers, mainly due to its asymptomatic nature and the resulting lack of early diagnosis. Cells with defects in DNA repair accumulate genetic abnormalities and may progress to become malignant. However, this DNA repair deficiency makes tumor cells vulnerable to further compromise by therapeutic targeting of other associated pathways, using agents such as poly-ADP ribose polymerase (PARP) inhibitors (PARPIs). A major challenge facing the use of PARPIs is the paucity of functional assays/biomarkers to identify HGSOC patients who may benefit from these agents, in particular the subgroup with non-BRCA-mutant, HR-deficient cancers. Our study presents a predictive tool which may help identify sporadic HGSOC patients, most likely to respond to PARPIs therapy. We have successfully developed and employed a functional 3D assay to test PARPIs sensitivity in EOC based on ascites-derived primary cell cultures (AsPCs) from EOC patients. Our data showed that this approach can better mimic primary tumor response to PARPIs treatments. We have successfully grown 42 AsPCs, and have prepared spheroid cultures from AsPCs using 3D-Biomatrix technology. We were able to monitor the cytotoxic effect on AsPCs spheroids of each of the drugs olaparib (Astra- Zeneca) and niraparib (Tesaro, licensed from Merck). Our results showed that AsPCs appear to be much more sensitive to niraparib compared to olaparaib. The cytotoxic effect observed by the two drugs was confirmed by analysis of γH2AX foci formation. Data demonstrated γH2AX foci to significantly increase in cell lines that are sensitive to the drug treatments. Consecutively, epithelial-to-mesenchymal transition (EMT) was also assessed in resistant vs. sensitive cell lines. Our results indicate that PARP inhibition can inhibit the acquisition of an EMT phenotype in sensitive cell lines, but not in resistant cell lines. Moreover, global gene and microRNA expression profiling of PARPI-R and PARPI-S spheroid cultures identifies gene/mRNA biomarkers, associated with PARPI sensitivity. We believe our predictive tool has helped classify genes that can be clinically relevant in identifying PARP inhibitor sensitivity in ovarian cancer.
2020-11-20 | GSE149940 | GEO
Project description:The pooled sample method is used in epigenomic research and expression analysis and is a cost-effective screening approach for small amounts of DNA. Evaluation of the pooled sample method in epigenomic studies is performed using the Illumina Infinium Methylation 450K BeadChip array; however, subsequent reports on the updated 850K array are lacking. A previous study demonstrated that the methylation levels obtained from individual samples were accurately replicated using pooled samples but did not address epigenome-wide association study (EWAS) statistics. The DNA quantification method, which is important for the homogeneous mixing of DNA in the pooled sample method, has since become fluorescence-based, and additional factors need to be considered including the resolution of batch effects of microarray chips and the heterogeneity of the cellular proportions from which the DNA samples are derived. In this study, four pooled samples were created from 44 individual samples, and EWAS statistics for differentially methylated positions (DMPs) and regions (DMRs) were conducted for individual samples and compared with the statistics obtained from the pooled samples.
2023-09-13 | GSE231532 | GEO