TY - JOUR
T1 - Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients
AU - Russo, Antonio
AU - Pantano, Francesco
AU - Loupakis, Fotios
AU - Zoccoli, Alice
AU - Iuliani, Michele
AU - Dell'Aquila, Emanuela
AU - Muda, Andrea Onetti
AU - Perrone, Giuseppe
AU - Brunelli, Chiara
AU - Schiavon, Gaia
AU - Ratta, Raffaele
AU - Ratta, Raffaele
AU - Correale, Pierpaolo
AU - Vincenzi, Bruno
AU - Falcone, Alfredo
AU - Tonini, Giuseppe
AU - Riva, Elisabetta
AU - Santini, Daniele
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10447/75250
M3 - Article
VL - 49
SP - 1501
EP - 1508
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -