Study of the apoptotic effect of urine as a diagnostic biomarker in patients with interstitial cystitis

Abstract

Introduction

The main objective of the study was to assess the apoptotic effect of urine from patients with interstitial cystitis (IC) in cell cultures and to study its value as a diagnostic biomarker for IC.

Material and methods

A prospective study was conducted between January 2010 and January 2015 and included 57 patients diagnosed with IC and 50 healthy patients from the Hospital Clinic of Barcelona and the La Paz University Hospital. The urine of these patients was exposed to cell cultures, and its ability to induce apoptosis in the cultures was analyzed. Using flow cytometry, we then measured the degree of apoptosis, quantified by the percentage of cells of the cell cycle in phase sub G0.

Results

The cell cultures exposed to the urine of patients with IC had a sub G1 peak and a G2 phase, which was significantly greater than that of the control group, and a significantly lower percentage in the S phase than the control group. The mean apoptosis values in the urine cultures from patients with IC were significantly higher than those of the control group. Using a value >10% of the apoptosis test as a positive result, we observed a specificity of 96% and a positive predictive value of 92%.

Conclusions

The urine of patients with IC exerts an apoptotic effect on tumor cell cultures that is significantly greater than that exerted by the urine of healthy control patients.

A ≥ 10% cutoff for the apoptosis test presented very low sensitivity (40%) but had a very high specificity (96%), thereby able to confirm the diagnosis of IC when positive.

Resumen

Introducción

El principal objetivo es valorar el efecto apoptótico de la orina de pacientes con cistitis intersticial (CI) en cultivos celulares y estudiar su valor como biomarcador diagnóstico para la CI.

Material y métodos

Estudio prospectivo entre enero de 2010 y enero de 2015, en el que se incluyeron 57 pacientes diagnosticadas de CI y 50 pacientes sanas del Hospital Clínic de Barcelona y del Hospital Universitario la Fe. Se expuso la orina de dichas pacientes a cultivos celulares y se analizó su capacidad para inducir apoptosis en ellos y posteriormente, mediante citometría de flujo, se midió el grado de apoptosis, cuantificado por el porcentaje de células del ciclo celular en fase sub G0.

Resultados

Los cultivos celulares expuestos a orina de pacientes con CI presentan un pico sub G1 y una fase G2, significativamente mayor que el grupo control, y en la fase S presentan un porcentaje significativamente menor al grupo control. Los valores medios de apoptosis en los cultivos de orina de pacientes con CI son significativamente muy superiores a los del grupo control. Para un valor > 10% de la prueba de apoptosis como resultado positivo, se observa una especificidad (96%) y un valor predictivo positivo (92%).

Conclusiones

La orina de pacientes con CI ejerce un efecto apoptótico sobre cultivos celulares tumorales significativamente superior al que ejercen orinas de pacientes controles sanos.

Un punto de corte ≥ 10% para la prueba de apoptosis presenta una sensibilidad muy baja (40%), pero tiene una especificidad muy alta (96%) pudiendo confirmar el diagnóstico de CI cuando es positiva.