1653P - Dicer and drosha expression and response to bevacizumab-based therapy in advanced colorectal cancer patients

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter Alice Zoccoli
Authors A. Zoccoli1, M. Iuliani1, F. Pantano1, G. Schiavon2, R. Ratta1, P. Correale3, A. Onetti Muda4, D. Santini1, G. Tonini1, B. Vincenzi5
  • 1Medical Oncology, university campus bio-medico, 00128 - rome/IT
  • 2Breast Unit, Erasmus MCDaniel den Hoed Cancer Center, NL-3075 EA - Rotterdam/NL
  • 3Medical Oncology Unit, Oncology Department, Azienda Ospedaliera Universitaria Senese, Siena/IT
  • 4Pathology Department, university campus bio-medico, 00128 - rome/IT
  • 5university campus bio-medico, 00128 - rome/IT

Abstract

Introduction

The miRNA-regulating enzyme 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 CRC patients.

Methods

We measured Dicer and Drosha messenger RNA (mRNA) levels in formalin-fixed paraffin-embedded specimens of advanced CRC treated with (n = 76) or without (n = 28) Bevacizumab-containing regimens and patients with diverticulosis (normal mucosa) (n = 20), using a quantitative reverse-transcriptase-polymerase-chain reaction assay, and compared the results with clinical outcome.

Results

We found that lower Dicer levels predicted a longer Progression-Free Survival (PFS) (P = .0001) and Overall Survival (OS) (P = .031) in Bevacizumab-treated patients. Conversely, Drosha levels were not associated with prognosis. Low Dicer levels were associated with better response to Bevacizumab-based treatments versus high Dicer levels (2.6% complete responses and 43.4% partial responses versus 1.3% and 28.9%, respectively; P = .045). Multivariate analysis identified three independent predictors of improved OS: high performance status [Relative Risk (RR) 1.56; P = .009], lower organs involvement (RR 0.72; P = .025) and low Dicer expression (RR 0.62; P = .009). Importantly, Dicer and Drosha expression did not correlate with outcome in not Bevacizumab-treated patients. Moreover we analysed Dicer and Drosha mRNA levels; our results showed a significantly higher Drosha expression in primary tumors than in normal mucosa (P = <.001), while Dicer levels did not differed.

Conclusions

These findings suggest that decreased Dicer mRNA levels seem to be independent predictors of favourable outcome and response in patients affected by advanced CRC treated with Bevacizumab-based therapy.

Disclosure

All authors have declared no conflicts of interest.