Dicer, Drosher mRNA levels linked to outcomes in ovarian cancer

Patients with ovarian cancer who had high levels of Dicer and Drosher messenger RNA had a median survival of greater than 11 years compared with a median survival of 2.66 years among patients with low levels of the proteins, according to recently published findings.

“Our findings have implications for the development of treatments for ovarian cancer that are based on RNA interference,” wrote researchers from The University of Texas M.D. Anderson Cancer Center.

The researchers used a quantitative reverse transcriptase-polymerase-chain-reaction assay to measure Dicer and Drosha levels in 111 patients with ovarian cancer and compared them with 11 benign epithelial-ovarian specimens.

Data indicated that decreased Dicer messenger RNA (mRNA) levels were an indicator of poor prognosis (HR=2.10; 95% CI, 1.15-3.85); however, low Drosha levels were not. Low levels of both Dicer and Drosha mRNA had a greater association with decreased survival (HR=4; 95% CI, 1.82 to 9.09) compared with levels of either protein alone.

Additional data indicated that low Dicer expression was also associated with advanced tumor stage (P=.007), and that low Drosha expression was associated with suboptimal surgical cytoreduction (P=.02). Further statistical analysis indicated that only three risk factors are independent predictors of survival among these patients — low Dicer levels (HR=2.10, P=.02), high-grade tumors (HR=2.46, P=.03) and poor response to chemotherapy (HR=3.95, P<.001).

Previous reports of Dicer and Drosha gene expression and survival rates in other cohorts of patients with ovarian, breast and lung cancer conveyed similar findings. – by Nicole Blazek

N Engl J Med. 2008; .359:2642-2650.

This report describes a highly provocative association between the amount of specific mRNA levels within tumor samples of women with epithelial ovarian cancer and clinical outcome. The investigators demonstrated a strong correlation between lower levels of Dicer mRNA and advanced stage disease and a similar relationship between low levels of Drosha expression and suboptimal surgical resection. These and other data in the report suggest the particular mRNAs investigated are related to important biological characteristics of the cancer. Further exploration in this complex area is indicated, with a particular focus on determining whether the findings could ultimately be employed to help select appropriate therapy for individual patients or possibly even be “targeted” as a strategy to favorably affect outcome.

– Maurie Markman, MD

HemOnc Today Editorial Board member