Serum matrix metalloproteinase 9 and colorectal neoplasia: a community-based evaluation of a potential diagnostic test

Abstract

Background:A blood test may be a more acceptable routine colorectal cancer (CRC) screening test than faecal occult blood test, flexible sigmoidoscopy or colonoscopy, and could be safer and cheaper. We evaluated the accuracy of a serum matrix metalloproteinase (MMP9) test for CRC in a non-presenting symptomatic population.Methods:A cohort, aged 50–69 with lower gastrointestinal symptoms, was identified by community-based survey. Accuracy of serum MMP9 was assessed by comparison with colonoscopy. Logistic regression identified predictors of neoplasia and receiver operating characteristic curve analyses determined the cutoff to maximise the sensitivity.Results:Data were available for 748 patients. Overall, 46 cases of neoplasia were identified. Univariate analysis demonstrated that demographic characteristics, behavioural factors, clinical symptoms and raised serum MMP9 concentration were all significantly associated with the presence of neoplasia. Our final logistic regression model had a sensitivity of 79% and specificity of 70%.Conclusion:We demonstrated a significant association between serum MMP9 concentration and the presence of neoplasia. Serum MMP9 levels are raised in those with cancer and high-risk adenomas, although MMP9 estimation is likely to have the greatest predictive utility when used as part of a panel of biomarkers. Further work is required to identify biomarkers that are sufficiently accurate for implementing into routine practice.

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

“…However, in another study including 63 CRC, 27 AA and 46 HC, 32 higher levels were found in neoplastic lesion samples, with no difference between CRC and AA. In a third study, 14 35 adenomas, 75 CRC and 70 HC were included. In this case, MMP levels were higher in CRC compared with adenomas or HC and in adenomas compared with HC.…”

“…34,35 This is particularly interesting since the major goal of screening is the detection of advanced colorectal neoplasms, including not only CRC but also AA. 25 Small NAA present low risk of transformation into CRC and are not considered an issue in CRC screening.…”

“…34 Conversely, and in accordance with our results, a large study including 3 CRC, 43 AA and 165 NAA by Wilson et al showed higher levels of serum MMP9 in the patients with advanced neoplasia than in those with non-advanced neoplasia, with a sensitivity and specificity of 79% and 63%, respectively. 35 Discrepancies between studies may be related to the number of patients included and the type of samples used, as some authors have pointed out. 13 Indeed, either serum 14,32 or plasma samples 16 have been used.…”

Neue Testverfahren in der Präventionsstrategie des kolorektalen Karzinoms

“…Sie weisen im Serum Genommutationen oder die entsprechend veränderten Proteinprodukte nach. Der Test zum Nachweis von Serum-Matrix-Metalloproteinase (MMP9) konnte immerhin bereits eine Sensitivität von 79 % und eine Spezifität von 70 % erreichen [35]. Ein anderer Test zum Nachweis hypermethylierter DNA des Septin-9-Gens im Serum weist eine Sensitivität von 63-72 % und eine Spezifität von 89-90 % auf [11,20].…”

Prognostic serum biomarkers for colorectal cancer – Review

“…In a very recent study, Wilson et al [24] evaluated the accuracy of MMP-9 for CRC in an asymptomatic population. From 748 patients overall, 46 cases of CRC were identified.…”