NanoString expression profiling in metastatic ovarian cancer
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ABSTRACT:
PROVIDER: PRJNA559825 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Most molecular characterizations of high-grade serous ovarian cancer (HGSOC) have been done in primary ovarian tumors. Such data may not be fully representative of HGSOC, which is characterized by widespread peritoneal metastases at the time of diagnosis and upon relapse. The most common site of HGSOC metastasis is the omentum. The omentum is characterized by strong immune and fibrotic activities and is a rich source of mesenchymal stem cells (MSCs), which have the capacity to differentiate into cancer-associated fibroblasts (CAFs) and promote ovarian cancer progression. The omentum is also rich in tertiary lymphoid structures (TLS), which are transient aggregates of leukocytes structurally and functionally comparable to secondary lymphoid tissues. Experimental design: With the goal of elucidating expression patterns in a large number of omental metastases, we profiled expression of immune- and cancer progression-related genes in pretreatment omental metastasis samples from 152 patients diagnosed with HGSOC.
2020-07-02 | GSE135712 | GEO
Project description:Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1. Total RNA was hybridised to NanoString miRNA Human v2.1 probes, immobilized to NanoString cartridge and analysed on the NanoString Digital Analyzer. NanoString nSolver Analysis Software was utilised to check QC metrics and extract raw miRNA counts. Expression was normalised for input using the housekeeping genes. Contributor: The Australian Ovarian Cancer Study Group
2015-05-19 | E-GEOD-65819 | biostudies-arrayexpress
Project description:CAF from metastatic ovarian cancer (mCAF) vs CAF from non-metastatic ovarian cancer (nmCAF)
| PRJNA798275 | ENA
Project description:To study feasibility of gene expression profiling from FFPE tissues using NanoString nCounter platform, we designed a pilot study utilizing samples from ovarian cancer cohort. We selected samples from large-scale epidemiologic studies and clinical trials representative of a wide variety of fixation times, block ages and block storage conditions. five serous carcinoma and six clear cell carcinoma samples with technical replicates
2014-07-01 | E-GEOD-55056 | biostudies-arrayexpress
Project description:To study feasibility of gene expression profiling from FFPE tissues using NanoString nCounter platform, we designed a pilot study utilizing samples from ovarian cancer cohort. We selected samples from large-scale epidemiologic studies and clinical trials representative of a wide variety of fixation times, block ages and block storage conditions.
2014-07-01 | GSE55056 | GEO
Project description:Breast and ovarian cancers, the most common cancers in women in India. Metastatic organotropism is a non-random, predetermined process which represents a more lethal and advanced form of cancer with increased mortality rate. In an attempt to study organotropism, salivary proteins were analyzed by mass spectrometry indicative of pathophysiology of breast and ovarian cancers compared to healthy and ovarian chemotherapy subjects. Collectively, 646 proteins were identified, of which 409 proteins were confidently identified across all four groups. Network analysis of up-regulated proteins such as coronin-1A, hepatoma derived growth factor, vasodilator-stimulated phosphoprotein (VASP), and cofilin in breast cancer and proteins like coronin-1A, destrin and HSP90α in ovarian cancer were functionally linked and were known to regulate cell proliferation and migration. Additionally, proteins namely VASP, coronin-1A, stathmin and suprabasin were confidently identified in ovarian chemotherapy subjects, possibly in response to combined paclitaxel and carboplatin drug therapy to ovarian cancer. In summary, this proteomic study was performed to identify a pattern of differentially expressed salivary proteins as indicators of metastatic organotropism potential of breast and ovarian cancers, as well as their response to neoadjuvant (paclitaxel and carboplatin) drugs therapy.
2020-05-26 | PXD011541 | Pride
Project description:High-grade serous (HGS) ovarian cancer is the most common and aggressive ovarian cancer type, and the most lethal gynaecological disease 1,2. The major cause is its highly metastatic nature and the limited availability of effective therapies to oppose it. The omentum is a highly vascularised visceral depot of adipose tissue with immune functions, which becomes the preferential metastatic site in patients with HGS ovarian cancer 1,2. The omentum provides an environment that supports the rapid growth of metastatic tumours and their spread within the peritoneal cavity and adjacent organs 2,3. Research aimed at understanding the biology of metastatic tumours in the omentum is therefore essential to find strategies to oppose HGS ovarian cancer. To this aim, there is the need for in vitro models that faithfully recapitulate the microenvironment of HGS omental metastasis in patients.
2023-11-28 | PXD042317 | Pride
Project description:High-grade serous (HGS) ovarian cancer is the most common and aggressive ovarian cancer type, and the most lethal gynaecological disease 1,2. The major cause is its highly metastatic nature and the limited availability of effective therapies to oppose it. The omentum is a highly vascularised visceral depot of adipose tissue with immune functions, which becomes the preferential metastatic site in patients with HGS ovarian cancer 1,2. The omentum provides an environment that supports the rapid growth of metastatic tumours and their spread within the peritoneal cavity and adjacent organs 2,3. Research aimed at understanding the biology of metastatic tumours in the omentum is therefore essential to find strategies to oppose HGS ovarian cancer. To this aim, there is the need for in vitro models that faithfully recapitulate the microenvironment of HGS omental metastasis in patients.
2023-11-28 | PXD042320 | Pride
Project description:Spheroid formation during epithelial ovarian cancer progression correlates with peritoneal organ colonization, disease recurrence, and poor prognosis. Although cancer progression has been demonstrated to be associated with and driven by metabolic changes within transformed cells, possible associations between metabolic dynamics and metastatic morphological transitions remain unexplored. To address this problem, performed quantitative proteomics was performed to identify protein signatures associated with three distinct morphologies (2D monolayers and two geometrically individual three-dimensional spheroidal states) of the high-grade serous ovarian cancer line OVCAR-3. Integrating the protein states into genome-scale metabolic models allowed the construction of context-specific metabolic models for each morphological stage of the OVCAR-3 cell line and systematically evaluate their metabolic functionalities.
2023-09-07 | PXD045194 | Pride
Project description:Iron accumulation in cancer cells contributes to malignant progression and chemoresistance. While disrupting this process can influence various hallmarks of cancer, the immunomodulatory effects of chelating iron in tumors remain undefined. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, elicits innate immune responses that control metastatic ovarian cancer. Deferiprone reprogrammed ovarian cancer cells towards an immunostimulatory state characterized by enhanced production of type I interferon (IFN) and surface overexpression of molecules that activate natural killer (NK) cells. Mechanistically, this reprogramming was driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses evoked upon iron chelation. Deferiprone administration synergized with chemotherapy and prolonged the survival of mice bearing metastatic ovarian cancer by bolstering intratumoral NK cell infiltration and type I IFN responses. Iron chelation may represent an alternative immunotherapeutic approach for malignancies that are normally refractory to T cell-centric modalities.
2024-06-26 | GSE246051 | GEO