Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients with Primary Ovarian Serous Carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30009 | GEO | 2012/04/19
SECONDARY ACCESSION(S): PRJNA143681
REPOSITORIES: GEO
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Project description:This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. We applied a customized TaqMan Low-Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma of Mullerian origin. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes.
2012-04-19 | E-GEOD-30009 | biostudies-arrayexpress
Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions. In the study presented here, effusion samples were obtained from 32 patients diagnosed with serous ovarian carcinoma (n=25), primary peritoneal serous carcinoma (n=6) or tubal serous carcinoma (n=1). They were accrued at the Division of Pathology in the Norwegian Radium Hospital from 2000-2006. RNA was used to study the expression profile of 381 multidrug resistant-related genes.
2011-11-17 | E-GEOD-29702 | biostudies-arrayexpress
Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions.
2011-11-17 | GSE29702 | GEO
Project description:Among the multidrug-resistant (MDR) clones of Mycobacterium tuberculosis (Mtb) that were epidemiologically particularly successful, the 100-32 MDR Beijing clone, also called B0/W148 clone, has emerged since the early sixties. These B0/W148 strains belonging to the lineage 2 within the global Mtb phylogeny, are the main contributors to the MDR epidemic in Russia and Eastern Europe, and since the USSR’s fall, have also propagated to Western Europe. Among the various mutations that were identified as being specific for the MDR B0/W148 clone, we focused on two found in the transcriptional regulators KdpDE and WhiB6 and characterized in a H37Rv strain background the transcriptional profile associated with these mutations and their potential impact on the in vitro and in vivo growth characteristics.
2024-09-25 | GSE269918 | GEO
Project description:Among the multidrug-resistant (MDR) clones of Mycobacterium tuberculosis (Mtb) that were epidemiologically particularly successful, the 100-32 MDR Beijing clone, also called B0/W148 clone, has emerged since the early sixties. These B0/W148 strains belonging to the lineage 2 within the global Mtb phylogeny, are the main contributors to the MDR epidemic in Russia and Eastern Europe, and since the USSR’s fall, have also propagated to Western Europe. Among the various mutations that were identified as being specific for the MDR B0/W148 clone, we focused on two found in the transcriptional regulators KdpDE and WhiB6 and characterized in a H37Rv strain background the transcriptional profile associated with these mutations and their potential impact on the in vitro and in vivo growth characteristics.
2024-09-25 | GSE269917 | GEO
Project description:PurposeThis study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy.Experimental designWe applied a customized TaqMan low density array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes.ResultsLeave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (OS; P = 0.06), four covariates (age, stage, CA125 level, and surgical debulking) do (P = 0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in OS prediction (log-rank statistic P < 0.003). The predictive power of this 11-gene signature was confirmed by dividing high- and low-risk patient groups, as defined by their clinical covariates, into four specific risk groups on the basis of expression levels.ConclusionThis study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer.
| S-EPMC3376649 | biostudies-literature
Project description:Resistance to chemotherapy is one of the most relevant aspects of treatment failure in cancer. Cell lines are used as models to study resistance. We analyze the transcriptional profile of two multidrug resistant (MDR) cell lines (Lucena 1 and FEPS) derived from the same drug-sensitive cell K562. Microarray data identified 130 differentially expressed genes (DEG) between K562 vs Lucena, 1,932 between K562 vs FEPS, and 1,211 between Lucena 1 versus FEPS. The NOTCH pathway was affected in FEPS with overexpression of NOTCH2 and HEY1. The highly overexpressed gene in MDR cell was ABCB1, and both presented the ABCB1 promoter unmethylated.
2015-01-01 | GSE57470 | GEO
Project description:Multidrug-resistant Klebsiella pneumoniae (MDR-KP) poses a significant global health threat, associated with high morbidity and mortality rates among hospitalized patients. The interaction between MDR-KP and its host is highly complex. Here, we explored these interactions in a mouse model of pneumonia using dual RNA-seq analysis.Our results revealed that, compared to the low-dose group, the high-dose group significantly upregulated hypoxia and pro-inflammatory cytokine-related genes in the host, and siderophore-related genes in the bacteria. Correlation analysis demonstrated a significant association between siderophore-related genes and clusters of genes related to pro-inflammatory cytokines and hypoxia.
2025-02-18 | GSE289556 | GEO
Project description:The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor LOX-1. OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotic.
2021-08-28 | GSE182766 | GEO
Project description:Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II-interacting Mediator complex. We previously identified an activator-targeted ~85 amino acid three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11 Mediator subunits in fungi. The Gal11 KIX domain is engaged by pleiotropic drug resistance transcription factor (Pdr1) orthologues, key regulators of the multidrug resistance (MDR) pathway in S. cerevisiae and in the clinically important human pathogen Candida glabrata. Drug-resistant clinical isolates of C. glabrata most commonly harbour point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway may represent a lynchpin in C. glabrata MDR. We have now carried out sequential biochemical and in vivo high-throughput screens to identify small molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation in both S. cerevisiae and C. glabrata and re-sensitizes drug-resistant C. glabrata to effective azole antifungal concentrations in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Samples are generated in triplicate for four conditions (DMSO/vehicle-treated, iKIX1-treated, DMSO/vehicle and ketoconazole-treated. and iKIX1-ketoconazole treated) in both Saccharomyces cerevisiae and Candida glabrata
2015-12-15 | E-GEOD-74361 | biostudies-arrayexpress