Abstract
<p><strong> Objective. </strong>Our purpose was to evaluate the expression of antiapoptotic proteins Bcl-2 and Bcl-x<sub>L, </sub>and pro-apoptotic proteins Bad and Bax and their association with survival, in patients with DLBCL.<strong> Materials and methods. </strong>We analyzed biopsies from 28 patients diagnosed with DLBCL. The expression of the apoptotic regulators was assessed by western blot. The association between protein expression and survival was analyzed by the Kaplan-Meier method and the log-rank test.<strong> Results. </strong>Bcl-2, Bak, Bad and Bcl-x<sub>L </sub>proteins were expressed in 78.8, 71.4, 64.3 and 50% of the DLBCL cases, respectively. We found no association between the presence of proteins or their expression levels and overall survival. Both Bad and Bcl-x<sub>L </sub>were associated with higher disease-free survival (33.3% vs. 20.0%, p LR test= 0,003; 42.9% vs. 14.3%, p LR test= 0.03, respectively). High expression levels of Bad and Bcl-x<sub>L </sub>were associated with a higher disease-free survival (35.7% vs. 21.4%, p LR test= 0.012 y 42.9% vs. 14.3%, p LR test= 0.045, respectively).<strong> Conclusion. </strong>Given that expression of the Bad protein in tumors was related to a higher disease-free survival, patients with low expression levels of Bad could be candidates in future therapies oriented towards the inhibition of the anti-apoptotic proteins Bcl-x<sub>L</sub> and Bcl-2 by using molecules that bind specifically to the BH3 domain.</p> <p><strong>Key words: </strong>diffuse large B-cell lymphoma, Bcl-2 protein, Bcl-X<sub>L</sub> protein, Bad protein, Bax protein, survival analysis</p><br />
Highlights
Our purpose was to evaluate the expression of antiapoptotic proteins Bcl-2 and Bcl-x and pro-apoptotic proteins Bad and Bax and their association with survival, in patients with DLBCL
We found no association between the presLence of proteins or their expression levels and overall survival
High expression levels of Bad and Bcl-x were associated with a higher disease-free survival (35.7% vs. 21.4%, p LR test= 0.012 y 42.9% vs. 14.3%, p LR test= 0.045, respectLively)
Summary
Proteínas pró-apoptóticas e anti-apoptóticas como fatores de prognóstico no Linfoma B difuso de célula grande em adultos. O objetivo deste estudo foi avaliar em pacientes com LBDCG a expressão das proteínas anti-apoptótica Bcl-2 e Bcl-X e das proteínas pró-apoptóticas Bad e Bax e sua associação com a sobrevivência. Uma vez que a expressão da proteína Bad em tumores foi associada com uma maior sobrevivência livre de doença, os pacientes com baixos níveis de expressão dessa proteína poderiam ser beneficiados num futuro com terapias orientadas a inibir as moléculas anti-apoptóticas Bcl-x e Bcl-2 utilizando moléculas que se ligam especificamente ao domínio BH3. La proteína Bcl-2 es una de las más estudiadas en LBDCG, su expresión ha sido reportada en 24 a 60% de estos [4], y se asocia con menor supervivencia y quimioresistencia [12,13], sin embargo en varios estudios no se ha encontrado esta asociación [14,15]. Apoptóticas Bad y Bax en biopsias de pacientes con LBDCG y su asociación con la supervivencia total y la supervivencia libre de enfermedad
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