Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE7556 | GEO | 2007/08/24
SECONDARY ACCESSION(S): PRJNA100375
REPOSITORIES: GEO
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Project description:Gene expression profiles were assessed for vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative (SKVCR 2.0) Experiment Overall Design: Duplicate gene expression microarray experiments were undertaken for each of SKOV3 and SKVCR 2.0. Comparative analysis between these two groups defined genes activated in vincristine resistance
2008-06-15 | E-GEOD-7556 | biostudies-arrayexpress
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. Gene expression profiles were obtained with the GeneChip® Human Genome U133 Plus 2.0 Array (Affymetrix, Singapore) according to the manufacturer´s instructions; all hybridization experiments were carried out in duplicate. The following samples were analyzed: human K562 cell line RNA from cells grown without drugs; human Lucena 1 cell line RNA from cells grown in medium with vincristine (Lucena 1+VCR); Lucena 1 cell line RNA from cells grown in medium without drugs (Lucena 1-VCR); human FEPS cell line RNA from cells grown in medium with daunorubicin (FEPS +DNR), and FEPS cell line RNA from cells grown in medium without drugs (FEPS -DNR).Comparisons of microarray expression data were carried out between K562 vs Lucena 1 grown in medium without vincristine; K562 vs FEPS grown in medium without daunorubicin; Lucena 1 grown in medium without vincristine vs FEPS grown in medium without daunorubicin. Additionally, we compared expression profiles of each multidrug resistant cell line (Lucena 1 and FEPS) grown in different conditions: Lucena 1 grown in medium without vincristine vs Lucena 1 grown in medium with vincristine, and FEPS grown in medium without daunorubicin vs FEPS grown in medium with daunorubicin.
2015-01-01 | E-GEOD-57470 | 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.
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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.
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