WashU Primary and Metastatic Tumors with Survival in High-Grade Serous Ovarian Cancer RNA-seq
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE218939 | GEO | 2023/04/27
REPOSITORIES: GEO
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Project description:High grade serous ovarian cancers (HGSC) are deadly malignancies that relapse despite carboplatin chemotherapy. Many commercially ovarian cancer cell lines are not good models for HGSC. Here we demonstrate that 3 low passage cell lines derived from HGSC have similar transcriptomes to their parental bulk tumors. These cell lines recapitulated tumor characteristics of the primary cancer and had responded to therapy in the same manner as primary HGSC cells, demonstrating they are accurate models for HGSCs. mRNA profiles of low passage high grade serous tumor cell lines and their parental tumors, generated by next generation sequencing, were compared.
2015-08-01 | E-GEOD-70073 | biostudies-arrayexpress
Project description:Low grade serous ovarian cancer (LGSC) is a rare subtype of ovarian cancer, characterized by a slow growth rate, resistance to current treatment regimens, multiple recurrences and poor survival. LGSC arise from serous borderline tumor (SBT), however the mechanism of transformation is poorly understood. To better understand the biology of serous ovarian tumors, we performed whole proteome profiling of LGSC, SBT and the more common high grade serous (HGSC) ovarian tumors. Proteins associated with the tumor microenvironment were differentially expressed between LGSC and SBT or HGSC. In particular, fibroblast activation protein (FAP), a protein expressed in cancer associated fibroblasts, is abundantly expressed in LGSC. Furthermore, Tregs and M2 macrophages are more abundant in the stroma of LGSC compared to SBT. Together these data suggest that the tumor microenvironment provides a supportive environment for LGSC tumorigenesis and progression, and that targeting the tumor microenvironment of LGSC may be a viable therapeutic strategy.
2024-08-15 | PXD046360 | Pride
Project description:High grade serous ovarian cancers (HGSC) are deadly malignancies that relapse despite carboplatin chemotherapy. Many commercially ovarian cancer cell lines are not good models for HGSC. Here we demonstrate that 3 low passage cell lines derived from HGSC have similar transcriptomes to their parental bulk tumors. These cell lines recapitulated tumor characteristics of the primary cancer and had responded to therapy in the same manner as primary HGSC cells, demonstrating they are accurate models for HGSCs.
2015-08-01 | GSE70073 | GEO
Project description:Precision medicine approaches in ovarian cancer require the accurate diagnosis of histotypes. In particular, there is a critical need to distinguish endometroid (EC) from high grade serous (HGSC) carcinomas, which differ greatly in outcomes, genetic predisposition and optimal treatment approaches. Herein, we performed label-free quantitative proteomics on freshly frozen tumour tissues to discover biomarkers that may distinguish EC from HGSC, and then used IHC to validate these using a contemporarily classified cohort of EC and HGSC samples.
2019-03-13 | PXD012998 | Pride
Project description:Profiling of loss of heterozygosity (LOH) in HGSC, subcrouping HGSC by LOH-based clustering and comparing to the LOH profiles of triple-negative breast cancer [previously submitted; GSE19594]. Study for the correlation of LOH burdern and LOH-based subgroups to clinical response to platinum-based chemotherapy in patients suffered from HGSC. SNP data (Affymetrix GenChip 250K SNP Nsp) from 47 high grade serous ovarian cancer were generated and used for LOH and copy number analysis, LOH-based hierarchical clustering to subclassify HGSC, and comparison to the chromosomal alterations in high grade brest cancer. The associstion between LOH-based subgroups and LOH burden and clinical resposne to platinum-based chemotherapy was investigated. The results were validated in two independent public opening datasets.
2012-11-06 | E-GEOD-39130 | biostudies-arrayexpress
Project description:Recent evidence suggests that ovarian high-grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp-TAg transgenic mouse, which expresses the SV40 large T-antigen (TAg) under the control of the mouse müllerian-specific Ovgp-1 promoter. Histologic analysis of the fallopian tubes of mogp-TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal appearing p53-positive epithelium that are similar to “p53 signatures” in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these noninvasive precursor lesions, we also identified invasive adenocarcinoma in the ovary of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp-TAg and WT C57BL/6. One of these genes, Top2a, which encodes topoisomerase II-alpha, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and specifically elevated in mouse STICs, but not in surrounding tissues. TOP2A protein was also found elevated in human STICs, low-grade, and high-grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumorigenesis, as well as for developing novel approaches for the prevention, diagnosis, and therapy of this disease. Keywords: transgenic mouse model, ovarian cancer, fallopian tube, intraepithelial carcinoma 6 mouse fallopian tubes (FT) were analyzed with experimental repeats; 3 wildtype C57BL6 mice (FT) and 3 transgenic mogp-TAg (FT), with one set of each at 7, 8 and 9 weeks of age.
2014-04-11 | E-GEOD-52011 | biostudies-arrayexpress
Project description:Ovarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53. In addition, the “p53 signature”, or overexpression of p53 protein (usually associated with mutation), is a potential precursor lesion of fallopian tube derived HGSC suggesting an essential role for p53 mutation in early serous tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected with a construct encoding for the R273H DNA binding domain mutation in p53, the most common mutation in HGSC. Mutation in p53 was not sufficient to transform MOE cells, but did significantly increase cell migration. A similar p53 mutation in murine ovarian surface epithelium (MOSE), another potential progenitor cell for serous cancer, was not sufficient to transform the cells nor change migration suggesting tissue specific effects of p53 mutation. Microarray data confirmed expression changes in pro-migratory genes in p53R273H MOE compared to parental cells, which could be reversed by suppressing Slug expression. Combining p53R273H with KRASG12V activation caused transformation of MOE into high-grade sarcomatoid carcinoma when xenografted into nude mice. Elucidating the specific role of p53R273H in the fallopian tube will improve understanding of changes at the earliest stage of transformation and could help develop chemopreventative strategies to prevent the accumulation of additional mutations and reverse progression of the “p53 signature” thereby, improving survival rates. We used a microarray to determine global changes in gene expression as a result of the p53 mutation specifically in mouse oviductal epithelium. Murine oviductal cells (MOE) were obtained from Dr. Barbara Vanderhyden at the University of Ottawa. Stable cell lines were generated using antibiotic resistant plasmids containing p53 R273H (Addgene, plasmid: 16439, donated by Dr. Vogelstein, Johns Hopkins University school of Medicine, Baltimore, MD) or pCMV-Neo (Origene PCMV6XL4, Rockville, MD). Total RNA was extracted from cell pellets collected from consecutive passages.
2014-10-25 | E-GEOD-62694 | biostudies-arrayexpress
Project description:Ovarian high-grade serous carcinoma (HGSC) accounts for the majority of deaths caused by epithelial ovarian cancer. The precise molecular changes attributable for the pathogenesis of HGSC are still largely unknown. TRAF4 has been identified to be up-regulated in some cancers. However, the association between TRAF4 and the malignancy of HGSC has not been elucidated before. In this study, we aim to explore the prognostic value and function of TRAF4 in HGSC. The results of immunohistochemistry in 174 cases of HGSC showed that high expression of TRAF4 was significantly associated with a shorter overall survival (p=0.005) and recurrence-free survival (p=0.003) in HGSC. Knock-down of TRAF4 inhibited the malignancy of ovarian cancer cells, and over-expression of TRAF4 increased cell malignancy both in vitro and in vivo. Moreover, mechanism studies demonstrated that TRAF4 promoted cell malignancy by activating YAP pathway in HGSC. In conclusion, TRAF4 could be a prognostic biomarker for HGSC and increase HGSC cell malignancy by activating YAP pathway, which may serve as a potential therapeutic target for HGSC.
2022-05-15 | GSE202840 | GEO
Project description:Our study presents the first genetic models of de novo high-grade serous carcinomas (HGSC) that originate in fallopian tube secretory epithelial cells and recapitulate the key genetic alterations and precursor lesions characteristic of human invasive ovarian cancer. Genomic copy number analysis, using array CGH, was performed on murine tumors in order to compare the overlap of copy number alterations between HGSC models and TCGA data. Array CGH was performed on genomic DNA isolated from murine HGSC tumors. Genomic DNA from three normal mouse fallopian tubes was pooled and used as the reference.
2013-12-17 | E-GEOD-49827 | biostudies-arrayexpress
Project description:Cisplatin- and carboplatin-resistant high-grade serous ovarian cancer (HGSC) cells were generated and new lines were created from single cell clones. All cells were derived from a common ancestral line, Ovcar4. RNA sequencing was performed to examine transcriptional changes related to acquisition of platinum resistance.
2022-08-01 | GSE141630 | GEO