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
Rok vydání: 2008
Předmět:
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