Detection of serum MMP-7 and MMP-9 in cholangiocarcinoma patients: evaluation of diagnostic accuracy

BACKGROUND Cholangiocarcinoma is an aggressive tumor with a tendency for local invasion and distant metastases. Timely diagnosis is very important because surgical resection (R0) remains the only hope for a cure. However, at present, there is no available tumor marker that can differentiate cholangiocarcinoma from benign bile duct disease. Previous studies have demonstrated that matrix metalloproteinase (MMP)-7 and MMP-9 are frequently expressed in cholangiocarcinoma specimens. METHODS This study was designed to determine whether the serum levels of MMP-7 and MMP-9 can discriminate cholangiocarcinoma patients from benign biliary tract disease patients in comparison to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). We measured the level of CEA, CA19-9, MMP-7 and MMP-9 in the serum of 44 cholangiocarcinoma and 36 benign biliary tract diseases patients. RESULTS Among the serum levels of CEA, CA19-9, MMP-7 and MMP-9, only the serum MMP-7 level was significantly higher in the patients with cholangiocarcinoma (8.9 +/- 3.43 ng/ml) compared to benign biliary tract disease patients (5.9 +/- 3.03 ng/ml) (p < 0.001). An receiver operating characteristic (ROC) curve analysis revealed that the detection of the serum MMP-7 level is reasonably accurate in differentiating cholangiocarcinoma from benign biliary tract disease patients (area under curve = 0.73; 95% CI = 0.614-0.848). While the areas under the curve of the ROC curves for CEA, CA19-9 and MMP-9 were 0.63 (95% CI = 0.501-0.760), 0.63 (95% CI = 0.491-0.761) and 0.59 (95% CI = 0.455-0.722), respectively. CONCLUSION Serum MMP-7 appears to be a valuable diagnostic marker in the discrimination of cholangiocarcinoma from benign biliary tract disease. Further prospective studies for serum MMP-7 measurement should be carried out to further investigate the potential of this molecule as a biomarker of cholangiocarcinoma.