Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

World J Gastroenterol. 2011 Mar 14;17(10):1373-8. doi: 10.3748/wjg.v17.i10.1373.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autoantibodies / chemistry*
  • Biomarkers / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / immunology*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cloning, Molecular
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / immunology*
  • Female
  • Humans
  • Isopropyl Thiogalactoside / pharmacology
  • Male
  • Matrix Metalloproteinase 7 / biosynthesis
  • Matrix Metalloproteinase 7 / immunology*
  • Middle Aged
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Autoantibodies
  • Biomarkers
  • Biomarkers, Tumor
  • Isopropyl Thiogalactoside
  • Matrix Metalloproteinase 7