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Inicio Actas Urológicas Españolas (English Edition) Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in p...
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Vol. 41. Issue 3.
Pages 172-180 (April 2017)
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Vol. 41. Issue 3.
Pages 172-180 (April 2017)
Original article
Expression of proteins FGFR3, PI3K, AKT, p21Waf1/Cip1 and cyclins D1 and D3 in patients with T1 bladder tumors: Clinical implications and prognostic significance
Expresión de las proteínas FGFR3, PI3K, AKT, p21Waf1/Cip1 y ciclinas D1 y D3 en pacientes con tumores de vejiga T1: implicaciones clínicas y significado pronóstico
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A.M. Blanca Pedregosaa, Á. Sánchez-Gonzáleza, J. Carrasco Valientea, J.M. Ruiz Garcíaa, E. Gómez Gómeza, A. López Beltránb, M.J. Requena Tapiaa,
Corresponding author
tapia3434@gmail.com

Corresponding author.
a Instituto Maimónides de Investigación Biomédica de Córdoba, Servicio de Urología del Hospital Universitario Reina Sofía, Córdoba, Spain
b Departamento de Especialidades Médico-Quirúrgicas, Facultad de Medicina, Universidad de Córdoba, Córdoba, Spain
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Table 1. Clinical and histopathological characteristics of patients with T1 bladder tumors.
Table 2. Analysis of early relapse-free survival in 40 cases of T1 bladder tumors using the Kaplan–Meier method and the Log-rank test.
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Abstract
Objective

To determine the differential protein expression of biomarkers FGFR3, PI3K (subunits PI3Kp110α, PI3KClassIII, PI3Kp85), AKT, p21Waf1/Cip1 and cyclins D1 and D3 in T1 bladder cancer versus healthy tissue and to study their potential role as early recurrence markers.

Material and method

This is a prospective study that employed a total of 67 tissue samples (55 cases of T1 bladder tumors that underwent transurethral resection and 12 cases of adjacent healthy mucosa). The protein expression levels were assessed using Western blot, and the means and percentages were compared using Student's t-test and the chi-squared test. The survival analysis was conducted using the Kaplan–Meier method and the log-rank test.

Results

Greater protein expression was detected for FGFR3, PI3Kp110α, PI3KClassIII, cyclins D1 and D3 and p21Waf1/Cip1 in the tumor tissue than in the healthy mucosa. However, these differences were not significant for PI3Kp85 and AKT. We observed statistically significant correlations between early recurrence and PI3Kp110α, PI3KClassIII, PI3Kp85 and AKT (P=.003, P=.045, P=.050 and P=.028, respectively), between the tumor type (primary vs. recurrence) and cyclin D3 (p=0.001), between the tumor size and FGFR3 (p=0.035) and between multifocality and cyclin D1 (p=0.039). The survival analysis selected FGFR3 (p=0.024), PI3Kp110α (p=0.014), PI3KClassIII (p=0.042) and AKT (p=0.008) as markers of early-recurrence-free survival.

Conclusions

There is an increase in protein expression levels in bladder tumor tissue. The overexpression of FGFR3, PI3Kp110α, PI3KClassIII and AKT is associated with increased early-recurrence-free survival for patients with T1 bladder tumors.

Keywords:
Bladder cancer
Protein expression
Western blot
Early recurrence
Resumen
Objetivo

Determinar la expresión proteica diferencial de los biomarcadores FGFR3, PI3K (subunidades PI3Kp110α, PI3KClassIII, PI3Kp85), AKT, p21Waf1/Cip1 y las ciclinas D1 y D3 en el cáncer de vejiga T1 versus tejido sano, así como estudiar su posible papel como marcadores de recidiva precoz.

Material y método

Se trata de un estudio prospectivo en el que se utilizaron un total de 67 muestras de tejido (55 casos de tumores de vejiga T1 sometidos a resección transuretral y 12 casos de mucosa sana adyacente). Los niveles de expresión de las proteínas se evaluaron mediante Western blot, y las medias y los porcentajes fueron comparados utilizando el test «t» de Student y la prueba Chi cuadrado. El análisis de supervivencia se realizó mediante el método Kaplan-Meier y el test Log-rank.

Resultados

Se detectó una mayor expresión proteica de FGFR3, PI3Kp110α, PI3KClassIII, ciclinas D1 y D3 y p21Waf1/Cip1 en tejido tumoral versus mucosa sana. Sin embargo, estas diferencias no fueron significativas para PI3Kp85 y AKT. Se observaron correlaciones estadísticamente significativas de PI3Kp110α, PI3KClassIII, PI3Kp85 y AKT con la recidiva temprana (p=0,003, p=0,045, p=0,050 y p=0,028 respectivamente), de ciclina D3 (p=0,001) con el tipo tumoral (primario versus recidivante), de FGFR3 (p=0,035) con el tamaño tumoral y de ciclina D1 (p=0,039) con la multifocalidad. El análisis de supervivencia seleccionó a FGFR3 (p=0,024), PI3Kp110α (p=0,014), PI3KClassIII (p=0,042) y AKT (p=0,008) como marcadores de supervivencia libre de recidiva precoz.

Conclusiones

Existe un incremento de los niveles de expresión proteica en el tejido tumoral vesical, asimismo, la sobreexpresión de FGFR3, PI3Kp110α, PI3KClassIII y AKT se asocia con una mayor supervivencia libre de recidiva precoz en pacientes con tumores de vejiga T1.

Palabras clave:
Cáncer de vejiga
Expresión proteica, Western blot
Recidiva precoz

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