Brief Article
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World J Gastroenterol. Mar 14, 2011; 17(10): 1373-1378
Published online Mar 14, 2011. doi: 10.3748/wjg.v17.i10.1373
Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma
Jing-Hua Zhou, Bin Zhang, Kemp H Kernstine, Li Zhong
Jing-Hua Zhou, Bin Zhang, Li Zhong, Department of Cell Biology, College of Life Sciences, Hebei University, Baoding 071400, Hebei Province, China
Kemp H Kernstine, Department of Thoracic Surgery, City of Hope Medical Center, Duarte, CA 91766, United States
Li Zhong, Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, United States
Author contributions: Zhou JH designed and performed the experiments, and prepared the manuscript; Zhang B partially assisted in conducting the experiments; Kernstine KH assisted with clinical samples and manuscript revision; Zhong L supervised the project and provided financial support for the experiments.
Supported by Science and Technology Projects of Hebei Province, #10396107D and NIH Grant CA137570 (Zhong L)
Correspondence to: Dr. Li Zhong, Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766, United States. lzhong@westernu.edu
Telephone: +1-909-4698220  Fax: +1-909-4695698
Received: December 9, 2010
Revised: January 13, 2011
Accepted: January 20, 2010
Published online: March 14, 2011
Abstract

AIM: To evaluate the diagnostic values of serum autoantibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC).

METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoantibodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the purified MMP-7 proteins. In addition, MMP-7 autoantibody levels in sera from 38 gastric cancer patients and from control serum samples were also tested.

RESULTS: The optimum conditions for recombinant MMP-7 protein expression were determined as 0.04 mmol/L Isopropyl-β-D-Thiogalactopyranoside (IPTG) induction at 37°C for four hours. The levels of serum autoantibodies against MMP-7 were significantly higher in patients with ESCC than in the matched-control samples (OD450 = 1.69 ± 0.08 vs OD450 = 1.55 ± 0.10, P < 0.001). The area under the receiver operating characteristic (ROC) curve was 0.87. The sensitivity and specificity for detection of ESCC were 78.0% and 81.0%, respectively, when the OD450 value was greater than 1.65. Although the levels of autoantibodies against MMP-7 were also significantly higher in patients with gastric cancer compared to control samples (OD450 = 1.62 ± 0.06 vs OD450 = 1.55 ± 0.10, P < 0.001), the diagnostic accuracy was less significant than in ESCC patients. The area of ROC curve was 0.75, whereas the sensitivity and specificity were 60.5% and 71.7%, respectively, when the cut-off value of OD450 was set at 1.60.

CONCLUSION: Serum autoantibody levels of MMP-7 may be a good diagnostic biomarker for esophageal squamous cell carcinoma.

Keywords: Matrix metalloproteinase-7; Serum autoantibody; Esophageal squamous cell carcinoma; Gastric cancer; Biomarker