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Abstract
BackgroundMatrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers.MethodsDifferences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies. Subsequently, we correlated these results with histopathological and clinical data of the patients.ResultsLuminex based expression analysis revealed a significant overexpression of MMP7 and an overexpression of MMP10 and MMP12 in the sera of colon cancer patients compared to the healthy control group. Patients with vascular invasion showed a significantly higher MMP12 expression than V0-staged patients. Moreover overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera displayed a significantly impaired overall survival. Multivariate analysis revealed high MMP10 serum levels to be an independent adverse prognostic marker in colon cancer patients.ConclusionsExpression patterns of MMP7, MMP10 and MMP12 in colon cancer patients´ sera are different compared to serum specimens of healthy individuals. Furthermore, overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera correlates with a dismal prognosis and may help to stratify patients into different risk groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2515-7) contains supplementary material, which is available to authorized users.
Highlights
Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation
We investigated multiplex bead-based immunoassay-technology measuring MMP7, MMP10 and MMP12 serum level in a homogenous collective of 78 patients suffering from colon cancer and a healthy control serum group to assess presumed differences in expression pattern and correlations with clinicopathological characteristics and survival
Taken together our results propose that MMP7, MMP10 and MMP12 are increased in sera of colon
Summary
Patients Serum samples of 78 patients with primary adenocarcinoma of the colon were included in our current study. Healthy serum samples were immediately stored at −80 °C after removal. Total protein concentration was measured using Pierce® BCA Protein Assay Kit (Thermo Fisher Scientific Inc, Rockford, IL, USA) and Infinite 200® PRO Reader (Tecan Group Ltd., Männedorf, Switzerland) according to the manufacturer’s protocol. Luminex based multiplex assay Serum samples for the detection of MMP7, MMP10 and MMP12 were processed using Milliplex MAP Human MMP Assay Kits (Merck Millipore, Millipore Corporation, Billerica, MA, USA) according to the manufacturer’s protocol. Multivariate analysis was performed using Cox proportional hazards regression including the following covariates: age, gender, UICC stage, TNM-classification, R-Stage, adjuvant chemotherapy, anastomotic leakage and relative serum expression of MMP7, MMP10 and MMP12 in colon cancer patientssera vs sera of healthy control serum group. Results were considered significant at a p-value less than 0.05
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