Whole exome DNA sequence profiling of spatial biopsies of high grade serous epithelial ovarian cancer
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PROVIDER: EGAS00001003048 | EGA |
REPOSITORIES: EGA
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Project description:We performed Array CGH on 25 patients with high grade serous epithelial ovarian cancer (HGS-EOC): each of this had multiple biopsies taken at the moment of the surgery in different anatomical sites, and 18 had also temporal biopsies taken after several cycles of chemotherapy. Blood was used as control. The experiment was performed to identify genomic alterations that can be used to classify the disease, going beyond the individual tumor heterogeneity.
2019-12-19 | E-MTAB-6900 | biostudies-arrayexpress
Project description:The prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Characterization of the TME often relies on a small representative tissue sample. However, the adequacy of such a sample for assessing components of the TME is not yet known. Here, we used immunohistochemical (IHC) staining and 7-color multiplex staining to evaluate CD8 (cluster of differentiation 8), CD68, PD-L1 (programmed death-ligand 1), CD34, FAP (fibroblast activation protein), and cytokeratin in 220 tissue cores from 26 high-grade serous ovarian cancer samples. Comparisons were drawn between a larger tumor specimen and smaller core biopsies based on number and location (central tumor vs. peripheral tumor) of biopsies. Our analysis found that the correlation between marker-specific cell subsets in larger tumor versus smaller core was stronger with two core biopsies and was not further strengthened with additional biopsies. Moreover, this correlation was consistently strong regardless of whether the biopsy was taken at the center or at the periphery of the original tumor sample. These findings could have a substantial impact on longitudinal assessment for detection of biomarkers in clinical trials.
| S-EPMC6879510 | biostudies-literature
Project description:This study aims at correlating changes in the transcriptional state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
2020-02-11 | E-MTAB-7083 | biostudies-arrayexpress
Project description:This study aims at correlating changes in the microRNA state in high grade serous epithelial ovarian cancer (HGS-EOC) to the response to therapy, in particular the insurgence of resistance to platinum-based treatment.
2020-02-11 | E-MTAB-7084 | biostudies-arrayexpress
Project description:Chemotherapy (CT) resistance in ovarian cancer is broad and encompasses diverse, unrelated drugs, suggesting more than one mechanism of resistance. We aimed to analyze the gene expression patterns in primary serous epithelial ovarian cancer (EOC) samples displaying different responses to first-line CT in an attempt to identify specific molecular signatures associated with response to CT. Initially, the expression profiles of 15 chemoresistant serous EOC tumors [time to recurrence (TTR) ≤6 months] and 10 chemosensitive serous EOC tumors (TTR ≥30 months) were independently analyzed which allowed the identification of specific sets of differentially expressed genes that might be functionally implicated in the evolution of the chemoresistant or the chemosensitive phenotype. Our data suggest that the intrinsic chemoresistance in serous EOC cells may be attributed to the combined action of different molecular mechanisms and factors linked with drug influx and efflux and cell proliferation, as possible implications of other molecular events including altered metabolism, apoptosis and inflammation cannot be excluded. Next, gene expression comparison using hierarchical clustering clearly distinguished chemosensitive and chemo- resistant tumors from the 25 serous EOC samples (training set), and consecutive class prediction analysis was used to develop a 43-gene classifier that was further validated in an independent cohort of 15 serous EOC patients and 2 patients with other ovarian cancer histotypes (test set). The 43-gene predictor set properly classified serous EOC patients at high risk for early (≤22 months) versus late (>22 months) relapse after initial CT. Thus, gene expression array technology can effectively classify serous EOC tumors according to CT response. The proposed 43-gene model needs further validation. 2 condition experiment: chemoresistant clinical samples versus chemosensitive samples
2011-07-23 | E-GEOD-28739 | biostudies-arrayexpress
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:Chemotherapy (CT) resistance in ovarian cancer is broad and encompasses diverse, unrelated drugs, suggesting more than one mechanism of resistance. We aimed to analyze the gene expression patterns in primary serous epithelial ovarian cancer (EOC) samples displaying different responses to first-line CT in an attempt to identify specific molecular signatures associated with response to CT. Initially, the expression profiles of 15 chemoresistant serous EOC tumors [time to recurrence (TTR) ≤6 months] and 10 chemosensitive serous EOC tumors (TTR ≥30 months) were independently analyzed which allowed the identification of specific sets of differentially expressed genes that might be functionally implicated in the evolution of the chemoresistant or the chemosensitive phenotype. Our data suggest that the intrinsic chemoresistance in serous EOC cells may be attributed to the combined action of different molecular mechanisms and factors linked with drug influx and efflux and cell proliferation, as possible implications of other molecular events including altered metabolism, apoptosis and inflammation cannot be excluded. Next, gene expression comparison using hierarchical clustering clearly distinguished chemosensitive and chemo- resistant tumors from the 25 serous EOC samples (training set), and consecutive class prediction analysis was used to develop a 43-gene classifier that was further validated in an independent cohort of 15 serous EOC patients and 2 patients with other ovarian cancer histotypes (test set). The 43-gene predictor set properly classified serous EOC patients at high risk for early (≤22 months) versus late (>22 months) relapse after initial CT. Thus, gene expression array technology can effectively classify serous EOC tumors according to CT response. The proposed 43-gene model needs further validation.
2011-07-24 | GSE28739 | GEO
Project description:Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.
| S-EPMC5645359 | biostudies-literature
Project description:Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes-associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC.
| S-EPMC4791205 | biostudies-literature
Project description:BackgroundThe major clinical challenge in the treatment of high-grade serous ovarian cancer (HGSOC) is the development of progressive resistance to platinum-based chemotherapy. The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the development of resistant disease.Methods and findingsEvolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide sequencing of 135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy. Samples were obtained from the clinical CTCR-OV03/04 studies, and patients were enrolled between 20 July 2007 and 22 October 2009. Median follow-up of the cohort was 31 mo (interquartile range 22-46 mo), censored after 26 October 2013. Outcome measures were overall survival (OS) and progression-free survival (PFS). There were marked differences in the degree of clonal expansion (CE) between patients (median 0.74, interquartile range 0.66-1.15), and dichotimization by median CE showed worse survival in CE-high cases (PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003). Bootstrap analysis with resampling showed that the 95% confidence intervals for the hazard ratios for PFS and OS in the CE-high group were greater than 1.0. These data support a relationship between heterogeneity and survival but do not precisely determine its effect size. Relapsed tissue was available for two patients in the CE-high group, and phylogenetic analysis showed that the prevalent clonal population at clinical recurrence arose from early divergence events. A subclonal population marked by a NF1 deletion showed a progressive increase in tumour allele fraction during chemotherapy.ConclusionsThis study demonstrates that quantitative measures of intra-tumour heterogeneity may have predictive value for survival after chemotherapy treatment in HGSOC. Subclonal tumour populations are present in pre-treatment biopsies in HGSOC and can undergo expansion during chemotherapy, causing clinical relapse.
| S-EPMC4339382 | biostudies-literature