MicroRNAs are posttranscriptional regulators of
messenger RNA synthesis that are intracellularly processed and transferred by the
microRNA-regulating machinery consisting of Drosha, Dicer, and Argonaute. The present study analyzed the expression and clinical role of the
microRNA-regulating machinery in advanced-stage ovarian
carcinoma. Drosha, Dicer, Argonaute 1, and Argonaute 2
messenger RNA levels were analyzed in 144 specimens (82 effusions, 33 primary
carcinomas, and 29 solid
metastases) using quantitative polymerase chain reaction. Dicer, Argonaute 1, and Argonaute 2
protein levels were analyzed in 103 of the above specimens by Western blotting. Argonaute 1, Argonaute 2, and Drosha messenger RNAs were overexpressed in effusions compared with primary
carcinomas and solid
metastases (P<.001), whereas Argonaute 1
protein expression was highest in solid
metastases (P=.004). Significantly higher expression of all 4 messenger RNAs was found in effusions compared with primary
carcinomas (P<.001 to P=.006), whereas Argonaute 2
messenger RNA (P=.002), Drosha
messenger RNA (P=.009), and Dicer
protein (P=.006) were overexpressed in solid
metastases compared with primary
carcinomas. Drosha, Dicer, Argonaute 1, and Argonaute 2 messenger RNAs and
protein levels in effusions were unrelated to clinicopathologic parameters. In primary
carcinomas, higher levels of 3 messenger RNAs were significantly associated with high-grade histology (P=.003 for Dicer and P=.01 for Drosha and Argonaute 1). Higher Argonaute 2
messenger RNA levels in prechemotherapy effusions were related to shorter progression-free survival (P=.049), a finding that retained its significance in multivariate Cox analysis (P=.046). In conclusion, Drosha, Dicer, Argonaute 1, and Argonaute 2 are differentially expressed at different metastatic sites in ovarian
carcinoma compared with primary
carcinomas, suggesting a role for these molecules in
tumor progression. Their clinical role in metastatic ovarian
carcinoma merits further research.