Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients

Antonio Russo, Francesco Pantano, Fotios Loupakis, Alice Zoccoli, Michele Iuliani, Emanuela Dell'Aquila, Andrea Onetti Muda, Giuseppe Perrone, Chiara Brunelli, Gaia Schiavon, Raffaele Ratta, Pierpaolo Correale, Bruno Vincenzi, Alfredo Falcone, Giuseppe Tonini, Elisabetta Riva, Daniele Santini

Risultato della ricerca: Article

16 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1501-1508
Numero di pagine8
RivistaEuropean Journal of Cancer
Volume49
Stato di pubblicazionePublished - 2013

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Colorectal Neoplasms
Mucous Membrane
Therapeutics
Ribonuclease III
Neoplasms
Messenger RNA
Survival
Diverticulum
MicroRNAs
Paraffin
Formaldehyde
Disease-Free Survival
Bevacizumab
Multivariate Analysis
Polymerase Chain Reaction
Control Groups

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cita questo

Russo, A., Pantano, F., Loupakis, F., Zoccoli, A., Iuliani, M., Dell'Aquila, E., ... Santini, D. (2013). Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients. European Journal of Cancer, 49, 1501-1508.

Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients. / Russo, Antonio; Pantano, Francesco; Loupakis, Fotios; Zoccoli, Alice; Iuliani, Michele; Dell'Aquila, Emanuela; Muda, Andrea Onetti; Perrone, Giuseppe; Brunelli, Chiara; Schiavon, Gaia; Ratta, Raffaele; Correale, Pierpaolo; Vincenzi, Bruno; Falcone, Alfredo; Tonini, Giuseppe; Riva, Elisabetta; Santini, Daniele.

In: European Journal of Cancer, Vol. 49, 2013, pag. 1501-1508.

Risultato della ricerca: Article

Russo, A, Pantano, F, Loupakis, F, Zoccoli, A, Iuliani, M, Dell'Aquila, E, Muda, AO, Perrone, G, Brunelli, C, Schiavon, G, Ratta, R, Correale, P, Vincenzi, B, Falcone, A, Tonini, G, Riva, E & Santini, D 2013, 'Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients', European Journal of Cancer, vol. 49, pagg. 1501-1508.
Russo, Antonio ; Pantano, Francesco ; Loupakis, Fotios ; Zoccoli, Alice ; Iuliani, Michele ; Dell'Aquila, Emanuela ; Muda, Andrea Onetti ; Perrone, Giuseppe ; Brunelli, Chiara ; Schiavon, Gaia ; Ratta, Raffaele ; Correale, Pierpaolo ; Vincenzi, Bruno ; Falcone, Alfredo ; Tonini, Giuseppe ; Riva, Elisabetta ; Santini, Daniele. / Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients. In: European Journal of Cancer. 2013 ; Vol. 49. pagg. 1501-1508.
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title = "Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients",
abstract = "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.",
author = "Antonio Russo and Francesco Pantano and Fotios Loupakis and Alice Zoccoli and Michele Iuliani and Emanuela Dell'Aquila and Muda, {Andrea Onetti} and Giuseppe Perrone and Chiara Brunelli and Gaia Schiavon and Raffaele Ratta and Pierpaolo Correale and Bruno Vincenzi and Alfredo Falcone and Giuseppe Tonini and Elisabetta Riva and Daniele Santini",
year = "2013",
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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 - 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 -