Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia

IntroductionMatrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia.ObjectiveTo assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels.MethodsWe analysed blood and tissue samples from patients with non-advanced adenomas (n = 25), advanced adenomas (n = 25), colorectal cancer (n = 25) and healthy controls (n = 75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia.ResultsPlasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3 ng/ml vs. 139.08 ng/ml, P < 0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6 ng/ml vs. 274.3 ng/ml, P = 0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r = 0.5, P < 0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173 ng/ml and 204 ng/ml (AUC = 0.80 [95% CI: 0.72–0.86], P < 0.001; sensitivity, 80–86% and specificity, 57–67%).ConclusionPlasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers.

ResumenIntroducciónLas metaloproteinasas (MMP) son proteínas que se sobreexpresan en diferentes etapas de la carcinogénesis colorrectal y podrían ser biomarcadores de neoplasia colorrectal.ObjetivoEvaluar la utilidad de MMP2 y MMP9 en plasma para detectar neoplasia colorrectal avanzada y su correlación con los niveles tisulares.MétodosSe analizaron muestras de sangre y tejido en pacientes con adenomas no avanzados (n = 25), adenomas avanzados (n = 25), cáncer colorrectal (n = 25) y controles sanos (n = 75). Los niveles plasmáticos y en tejido se determinaron mediante tecnología xMAP Luminex y zimografía con gelatina. Se utilizaron curvas ROC para calcular el punto de corte óptimo para neoplasia colorrectal avanzada.ResultadosLos niveles de MMP2 fueron similares en las distintas lesiones. Los niveles de MMP9 fueron significativamente superiores en los pacientes con lesiones neoplásicas comparados con controles sanos (mediana de 292,3 ng/ml vs. 139,08 ng/ml; p < 0,001). Los niveles de MMP9 fueron más altos en los cánceres colorrectales que en adenomas no avanzados (mediana de 314,6 ng/ml vs. 274,3 ng/ml; p = 0,03). Se observó correlación entre los niveles plasmáticos y tisulares de MMP9 (r = 0,5; p < 0,001). El rango de MMP9 plasma con mayor precisión diagnóstica fue 173–204 ng/ml (AUC = 0,80 [IC 95%: 0,72–0,86], p < 0,001; sensibilidad 80–86% y especificidad 57–67%).ConclusiónLos niveles en plasma de MMP9 podrían ser un biomarcador útil para detectar neoplasia colorrectal avanzada. La combinación con otros biomarcadores podría aumentar su rendimiento diagnóstico.