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.

Figure 1

Plasma MMP-7 (A) and plasma CA19-9 (B) levels in patients with (peri)pancreatic carcinoma (●) compared with those with benign disease (□) according to pathology. ■, patients who underwent pancreatic resection for suspected malignancy, which turned out to be pancreatitis at pathology. Line, median plasma MMP-7 or CA19-9 level. Median and interquartile range of plasma MMP-7 in patients with (peri)pancreatic carcinoma versus those with benign disease was 1.95 ng/mL (interquartile range, 0.81–3.22 ng/mL) versus 0.83 ng/mL (interquartile range, 0.25–1.21 ng/mL), and of plasma CA19-9, 28 units/mL (interquartile range, 0–169 units/mL) versus 0 units/mL (interquartile range, 0–5.5 units/mL), respectively.

Figure 2

Receiver operating characteristic curve of plasma MMP-7 and CA19-9 for the detection of (peri)pancreatic carcinoma. Area under the curve for MMP-7 is 0.73 (95% CI, 0.63–0.84) and for CA19-9, 0.75 (95% CI, 0.64–0.85).