Evaluation of Matrix Metalloproteinase 7 in Plasma and Pancreatic Juice as a Biomarker for Pancreatic Cancer

Abstract

Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81-3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25-1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18-241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5-99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today's most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63-0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64-0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not sufficient to determine treatment strategy in patients with a periampullary mass, but combined evaluation of plasma MMP-7 with CA19-9 and other markers may be clinically useful. (Cancer Epidemiol Biomarkers Prev 2007;16(5):886-91)

Pilot Study of Blood Biomarker Candidates for Detection of Pancreatic Cancer

“…Indeed, 4 of the 12 candidates had been previously tested for pancreatic cancer biomarker, including OPN (osteopontin) 16 , CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) 17 , MMP 7 (matrix metalloproteinase 7) 18 , and LCN 2 (lipocalin 2) 19 . These 4 candidates were included in our study for re-evaluation as individual markers, as well as their performance in a composite biomarker panel, which had not been previously performed.…”

Membranous type matrix metalloproteinase 16 induces human prostate cancer metastasis

“…The expression of MMPs has been reported to be upregulated in various types of cancer, including in lung, pancreatic, breast and prostate cancer (20)(21)(22)(23)(24)(25)(26). While the majority of studies were mainly focused on the collagenase and gelatinase MMPs, studies on the membrane type MMPs are limited (27)(28)(29).…”

Adipokines and Cytokines in Human Pancreatic Juice: Unraveling the Local Pancreatic Inflammatory Milieu

“…Basic analyses of bicarbonate, amylase, and lipase concentrations to determine pancreatic exocrine function are well established [3,15]. Investigators have also evaluated pancreatic juice for the presence of tumor markers [4,5,16], more recently using complex proteomic analyses to identify novel potential markers of malignancy [17,18], and even to distinguish between cancer and pancreatitis [19].…”

“…For many years, pancreatic juice has been used as a ''window'' to evaluate local pancreatic pathology. Pancreatic exocrine function, tumor markers, genetic mutations, and several other molecules of interest have been evaluated [3][4][5]. However, remarkably few investigators have studied pancreatic juice for the purpose of measuring the mediators of pancreatic inflammation.…”