Serum CA19-9, cathepsin D, and matrix metalloproteinase-7 as a diagnostic panel for pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) accounts for 95% of pancreatic cancers. CA19-9 is not widely used for screening PDAC due to its low sensitivity. Here, we studied the clinical usefulness of cathepsin D, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) for screening patients with PDAC. A total of 248 patients with PDAC and 216 control subjects were recruited (109 PDAC patients and 70 controls in the training set and 139 PDAC patients and 146 controls in the validation set). We measured serum levels of cathepsin D, TIMPs (-1, -3, and -4), and MMPs (-1, -7, -8, and -9) using Fluorokine MAP multiplex kits. The concentrations of cathepsin D and MMP-7 were significantly higher in PDAC subjects than control subjects. In the training set, the diagnostic sensitivity and AUC of the panel of CA19-9, cathepsin D, and MMP-7 for PDAC were increased to 88% and 0.900, compared to 74% and 0.835 of CA19-9 single marker at 80% specificity. The sensitivity using cut-off value of biomarker panel was significantly increased in the validation set as well as training set. Our findings indicate that a serum biomarker panel consisting of CA19-9, cathepsin D, and MMP-7 may provide the most effective screening test currently feasible for PDAC.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hyung-Doo
HD
Park
Eun-Suk
ES
Kang
Jong-Won
JW
Kim
Kyu-Taek
KT
Lee
Kwang Hyuck
KH
Lee
Young Suk
YS
Park
Joon-Oh
JO
Park
Jeeyun
J
Lee
Jin Seok
JS
Heo
Seong Ho
SH
Choi
Dong Wook
DW
Choi
Seonwoo
S
Kim
Jong Kyun
JK
Lee
Soo-Youn
SY
Lee
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018395:CA-19-9 Antigen / Q000097:blood*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis*; D002402:Cathepsin D / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*
D018395:CA-19-9 Antigen; D002402:Cathepsin D; D020783:Matrix Metalloproteinase 7