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Dicer, Drosha, and outcomes in patients with ovarian cancer

William M Merritt1, Yvonne G Lin, Liz Y Han

  • 1University of Texas M.D. Anderson Cancer Center, Houston, TX 77230, USA.

The New England Journal of Medicine
|December 19, 2008
PubMed
Abstract

Insights

Reduced levels of Dicer and Drosha RNA interference machinery components are linked to poorer outcomes in ovarian cancer patients. High expression of both Dicer and Drosha correlates with significantly longer survival, highlighting their prognostic value.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian cancer is a significant health concern with complex molecular underpinnings.
  • The RNA-interference (RNAi) machinery, including Dicer and Drosha, plays a crucial role in gene regulation.
  • Dysregulation of RNAi components may contribute to ovarian cancer development and progression.

Purpose of the Study:

  • To investigate the expression levels of Dicer and Drosha in ovarian cancer.
  • To correlate Dicer and Drosha expression with clinical outcomes and patient survival.
  • To explore the potential prognostic significance of these RNAi components in ovarian cancer.

Main Methods:

  • Quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay to measure Dicer and Drosha mRNA levels in 111 ovarian cancer specimens.
  • Validation using published microarray data from ovarian, breast, and lung cancer cohorts.
  • Mutational analysis of Dicer and Drosha genes and in vitro functional assays using small interfering RNA (siRNA) and short hairpin RNA (shRNA).

Main Results:

  • Dicer and Drosha mRNA levels were decreased in 60% and 51% of ovarian cancer specimens, respectively.
  • Low Dicer expression correlated with advanced tumor stage, and low Drosha expression with suboptimal surgical cytoreduction.
  • High co-expression of Dicer and Drosha was associated with significantly longer median survival (>11 years vs. 2.66 years).
  • Low Dicer expression, high-grade histology, and poor chemotherapy response were independent predictors of reduced disease-specific survival.

Conclusions:

  • Dicer and Drosha mRNA levels are significantly associated with clinical outcomes in ovarian cancer patients.
  • These RNAi components may serve as potential prognostic biomarkers for ovarian cancer.
  • Further research into the functional roles of Dicer and Drosha in ovarian cancer pathogenesis is warranted.

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