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RESEARCH PRODUCT

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

Alfredo FalconeElisabetta RivaAntonio RussoRaffaele RattaFrancesco PantanoFotios LoupakisTonini GiuseppeMichele IulianiPierpaolo CorrealeEmanuela Dell'aquilaSantini DanieleAlice ZoccoliChiara BrunelliGiuseppe PerroneVincenzi BrunoGaia SchiavonAndrea Onetti Muda

subject

MaleRibonuclease IIICancer ResearchSettore MED/06 - Oncologia Medicagenetic processesAngiogenesis InhibitorsKaplan-Meier EstimateDEAD-box RNA HelicasesangiogenesisIntestinal MucosaOligonucleotide Array Sequence AnalysisAged 80 and overReverse Transcriptase Polymerase Chain Reactionfood and beveragesMiddle AgedPrognosisImmunohistochemistryCRCBevacizumabGene Expression Regulation NeoplasticqPCRTreatment OutcomeOncologyMonoclonalImmunohistochemistryFemaleColorectal Neoplasmsmedicine.drugAdultBevacizumabBiologyAntibodies Monoclonal HumanizedDroshaYoung AdultSDG 3 - Good Health and Well-beingmicroRNAmedicineHumansDroshamiRNAAgedGene Expression ProfilingfungiCancermedicine.diseaseGene expression profilingenzymes and coenzymes (carbohydrates)miRNA; angiogenesisMultivariate AnalysisCancer researchbiology.proteinBevacizumab; CRC; Dicer; Drosha; miRNAs; qPCRDicerDicer

description

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.

yearjournalcountryeditionlanguage
2013-01-01
http://hdl.handle.net/11568/208716