Dicer, Drosha, and outcomes in patients with ovarian cancer
Autor: | Whitney A. Spannuth, Menashe Bar-Eli, William M. Merritt, Alpa M. Nick, Anil K. Sood, Marc E. Lenburg, Hua Wang, Samuel C. Mok, Michael T. Deavers, Gabriel Lopez-Berestein, Liz Y. Han, Alexandra A. Mourad-Zeidan, Len A. Pennacchio, Joe W. Gray, Peter R. Mueller, Michael J. Birrer, Rosemarie Schmandt, Yvonne G. Lin, Diana L. Urbauer, Robert L. Coleman, Aparna A. Kamat, Jan Fang Cheng |
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Rok vydání: | 2008 |
Předmět: |
Adult
Ribonuclease III Small interfering RNA Lung Neoplasms DNA Mutational Analysis Mutation Missense Breast Neoplasms Kaplan-Meier Estimate Transfection XPO5 Article Small hairpin RNA DEAD-box RNA Helicases Cell Line Tumor microRNA Endoribonucleases medicine Humans Neoplasms Glandular and Epithelial RNA Messenger RNA Small Interfering Drosha Aged Neoplasm Staging Aged 80 and over Ovarian Neoplasms biology business.industry Reverse Transcriptase Polymerase Chain Reaction Cancer General Medicine Middle Aged medicine.disease Prognosis Gene Expression Regulation Neoplastic MicroRNAs Treatment Outcome Immunology Multivariate Analysis biology.protein Cancer research Female RNA Interference Ovarian cancer business Dicer |
Zdroj: | Merritt, W.M.; Lin, Y.G.; Han, L.Y.; Karnat, Aa.; Spannuth, W.A.; Schmandt, R.; et al.(2008). Dicer, Drosha, and outcomes in patients with ovarian cancer. New England Journal of Medicine, 359. Lawrence Berkeley National Laboratory: Lawrence Berkeley National Laboratory. Retrieved from: http://www.escholarship.org/uc/item/2t74z8db |
ISSN: | 1533-4406 |
Popis: | BACKGROUND: We studied Dicer and Drosha, components of the RNA-interference machinery, in ovarian cancer. METHODS: We measured messenger RNA (mRNA) levels of Dicer and Drosha in specimens of invasive epithelial ovarian cancer from 111 patients, using a quantitative reverse-transcriptase-polymerase-chain-reaction assay, and compared the results with clinical outcomes. Validation was performed with the use of published microarray data from cohorts of patients with ovarian, breast, and lung cancer. Mutational analyses of genomic DNA from the Dicer and Drosha genes were performed in a subgroup of ovarian-cancer specimens. Dicer-dependent functional assays were performed by means of in vitro transfection with small interfering RNA (siRNA) and short hairpin RNA (shRNA). RESULTS: Levels of Dicer and Drosha mRNA correlated with the levels of expression of the corresponding protein and were decreased in 60percent and 51percent of ovarian-cancer specimens, respectively. Low Dicer expression was significantly associated with advanced tumor stage (P=0.007), and low Drosha expression with suboptimal surgical cytoreduction (P=0.02). Cancer specimens with both high Dicer expression and high Drosha expression were associated with increased median survival (>11 years, vs. 2.66 years for other subgroups; P |
Databáze: | OpenAIRE |
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