Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma.

AIM To determine whether the serum level of matrix metalloproteinase-7 (MMP7) has the potential to diagnosis cholangiocarcinoma from benign biliary tract diseases. METHODS This study was performed according to the PRoBE (a prospective-specimen-collection, retrospective-blinded-evaluation) design. A total of 187 patients with obstructive jaundice were consecutively enrolled. After the diagnostic status of these patients was ascertained, their levels of serum MMP7 were assayed and compared with serum carbohydrate antigen 19-9 (CA19-9). This was conducted in a blinded case (cholangiocarcinoma)-control (benign biliary tract disease) setup. RESULTS MMP7 and CA19-9 serum levels were significantly elevated in cholangiocarcinoma patients (P < 0.001). The area under the curve (AUC) from a receiver operating characteristic (ROC) curve analysis for the diagnosis of cholangiocarcinoma, using MMP7 was more accurate than CA19-9 (AUC = 0.84, 95% CI: 0.778-0.903 for MMP7 and AUC = 0.79, 95% CI: 0.708-0.868 for CA19-9). The sensitivity and specificity of serum MMP7 (cut-off value of 5.5 ng/mL) was 75% and 78%, respectively, while the sensitivity and specificity of serum CA19-9 (cut-off value of 100 U/mL) was 68% and 87%, respectively. CONCLUSION Serum values of MMP7 and CA19-9 appear to be useful biomarkers for differentiating cholangiocarcinoma from benign biliary tract obstructive diseases.

[1]  J. Wu,et al.  Elevated Serum Matrix Metalloproteinase-3 and -7 in H. pylori-Related Gastric Cancer Can Be Biomarkers Correlating with a Poor Survival , 2010, Digestive Diseases and Sciences.

[2]  K. Leelawat,et al.  Detection of serum MMP-7 and MMP-9 in cholangiocarcinoma patients: evaluation of diagnostic accuracy , 2009, BMC gastroenterology.

[3]  Holly Janes,et al.  Pivotal Evaluation of the Accuracy of a Biomarker Used for Classification or Prediction: Standards for Study Design , 2008, Journal of the National Cancer Institute.

[4]  P. Bossuyt STARD statement: still room for improvement in the reporting of diagnostic accuracy studies. , 2008, Radiology.

[5]  Yvonne Vergouwe,et al.  Bmc Medical Research Methodology Open Access Advantages of the Nested Case-control Design in Diagnostic Research , 2022 .

[6]  P. Brown,et al.  Systematic Evaluation of Candidate Blood Markers for Detecting Ovarian Cancer , 2008, PloS one.

[7]  D. M. Lloyd,et al.  Elevation of Carbohydrate Antigen 19.9 in Benign Hepatobiliary Conditions and Its Correlation with Serum Bilirubin Concentration , 2008, Digestive Diseases and Sciences.

[8]  M. Nagino,et al.  Expression of matrix metalloproteinase 7 is an unfavorable postoperative prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts. , 2008, Human pathology.

[9]  T. Shim,et al.  Is metalloproteinase-7 specific for idiopathic pulmonary fibrosis? , 2008, Chest.

[10]  C. Pairojkul,et al.  Cholangiocarcinoma: lessons from Thailand , 2008, Current opinion in gastroenterology.

[11]  Y. Nimura,et al.  Immunohistochemical analysis of the progression of flat and papillary preneoplastic lesions in intrahepatic cholangiocarcinogenesis in hepatolithiasis , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[12]  C. Nadal,et al.  Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients , 2007, International journal of cancer.

[13]  J. Bridgewater,et al.  New advances in the management of biliary tract cancer. , 2007, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[14]  K. Leelawat,et al.  Circulating hTERT mRNA as a tumor marker in cholangiocarcinoma patients. , 2006, World journal of gastroenterology.

[15]  Hiroyuki Yamamoto,et al.  Role of Matrix Metalloproteinase-7 (Matrilysin) in Human Cancer Invasion, Apoptosis, Growth, and Angiogenesis , 2006, Experimental biology and medicine.

[16]  S. N. Agoff,et al.  Biliary brush cytology and the detection of cholangiocarcinoma in primary sclerosing cholangitis: evaluation of specific cytomorphologic features and CA19-9 levels. , 2005, American journal of clinical pathology.

[17]  J. Neoptolemos,et al.  Comprehensive Analysis of Matrix Metalloproteinase and Tissue Inhibitor Expression in Pancreatic Cancer , 2004, Clinical Cancer Research.

[18]  G. Grazi,et al.  Mirizzi syndrome with cholecysto-choledocal fistula with a high CA19-9 level mimicking biliary malignancies: a case report. , 2003, Hepato-gastroenterology.

[19]  Hiroyuki Yamamoto,et al.  Association of trypsin expression with tumour progression and matrilysin expression in human colorectal cancer , 2003, The Journal of pathology.

[20]  Johannes B Reitsma,et al.  The STARD initiative , 2003, The Lancet.

[21]  N. Afdhal,et al.  Cholangiocarcinoma of the hepatic hilum (Klatskin tumor) , 2002, Current treatment options in gastroenterology.

[22]  S. Kawasaki,et al.  Matrix metalloproteinase‐7 expression and biologic aggressiveness of cholangiocellular carcinoma , 2002, Cancer.

[23]  G. Gores,et al.  The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis , 2000, American Journal of Gastroenterology.

[24]  Y. Okada,et al.  Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers , 1999, Gut.

[25]  H. Yamamoto,et al.  Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. , 1999, Cancer research.

[26]  G. Gores,et al.  Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis. , 1993, Mayo Clinic proceedings.

[27]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.

[28]  David E Bruns,et al.  The STARD initiative and the reporting of studies of diagnostic accuracy. , 2003, Clinical chemistry.

[29]  M. Mareel,et al.  Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. , 2001, Journal of cell science.