Purpose: The miRNA-regulating enzymes Dicer and Drosha exhibit aberrant expression in several cancer types. Dicer and Drosha play a crucial role during the angiogenetic process in vitro and, for Dicer, in vivo. We aimed to investigate the potential role of Dicer and Drosha in predicting response to Bevacizumab-based therapy in advanced colorectal cancer (CRC) patients. Methods: Dicer and Drosha mRNA levels were analysed in formalin-fixed paraffin-embedded specimens from patients affected by advanced CRC treated with or without Bevacizumab-containing regimens (n = 116 and n = 50, respectively) and from patients with diverticulosis as control group (n = 20). The experimental data were obtained using qRT-PCR, analysed comparing Dicer and Drosha expression levels in tumour samples versus normal mucosa and then compared to clinical outcome. Results: The tumour samples from Bevacizumab-treated patients showed a significantly higher Drosha expression (P <.001) versus normal mucosa, while Dicer levels did not differ. Intriguingly, we found that low Dicer levels predicted a longer progression-free survival (PFS) (P <.0001) and overall survival (OS) (P =.009). In addition, low Dicer levels were associated with better response to Bevacizumab-based treatments versus high Dicer levels (1.7% complete responses and 53.4% partial responses versus 0% and 32.7%, respectively; P =.0067). Multivariate analysis identified three independent predictors of improved OS: high performance status (PS) (relative risk (RR) 1.45; P =.011), lower organs involvement (RR 0.79; P =.034) and low Dicer expression (RR 0.71; P =.008). Conversely, Drosha levels were not associated with prognosis and outcome associated with treatment. In non-Bevacizumab-treated patients, Dicer and Drosha expression did not correlate with outcome. Conclusion: These findings suggest that low Dicer mRNA levels seem to be independent predictors of favourable outcome and response in patients affected by advanced CRCs treated with Bevacizumab-based therapy.

Bevacizumab, CRC, Dicer, Drosha, miRNAs, qPCR
dx.doi.org/10.1016/j.ejca.2012.11.014, hdl.handle.net/1765/39870
European Journal of Cancer
Erasmus MC: University Medical Center Rotterdam

Vincenzi, B, Zoccoli, A, Schiavon, G, Iuliani, M, Pantano, F, Dell'Aquila, E, … Tonini, G. (2013). Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients. European Journal of Cancer, 49(6), 1501–1508. doi:10.1016/j.ejca.2012.11.014