title: Combined evaluation of matrix metalloproteinases and their inhibitors has better clinical utility in oral cancer.
abstract: BACKGROUND
  Oral cancer is a major health hazard worldwide with increasing incidence and mortality. Cervical lymph node metastasis is a major determinant of outcome in oral cancer. The matrix metalloproteinase (MMP) system is critically involved in invasion and metastasis. Assessment of MMPs and tissue inhibitors of MMPs (TIMPs) in certain combinations might have better clinical efficacy given their potential role in the metastatic process.
  
  
  OBJECTIVE
  Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 50 controls and 75 oral cancer patients (nonmetastatic, n=54; metastatic, n=21) were evaluated to assess their investigative value and role in predicting the behavior of this malignancy.
  
  
  METHODS
  The plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were quantified by ELISA. The best 2- and 3-marker combinations were calculated using the statistical software mROC. The diagnostic values for all the biomolecules as single markers and their combinations were estimated using the measures of diagnostic accuracy, i.e. the area under the ROC curve and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 95% limits of sensitivity and specificity, respectively.
  
  
  RESULTS
  MMP-9, TIMP-1 and TIMP-2 were significantly elevated (p=0.000, p=0.013 and p=0.005, respectively) in oral cancer patients. MMP-9 emerged as the best single statistically significant marker in plasma for oral cancer detection. It showed an increase in diagnostic performance when tested in combination with MMP-2 and TIMP-2. The median plasma MMP-9 levels were elevated in both the metastatic and nonmetastatic groups compared with controls (p<0.004 and p<0.007, respectively).
  
  
  CONCLUSIONS
  The results indicated that plasma MMP and TIMP levels in relevant combinations may facilitate clinical decisionmaking for improved management of oral cancer patients and may provide important data for selecting patients for treatment with drugs that interfere with MMP and TIMP activities.
authors.affiliation: Biochemistry Research Division, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India.
authors.forename: Ragini D
authors.initials: RD
authors.lastname: Singh
authors.forename: Haridas
authors.initials: H
authors.lastname: Nilayangode
authors.forename: Jayendra B
authors.initials: JB
authors.lastname: Patel
authors.forename: Franky D
authors.initials: FD
authors.lastname: Shah
authors.forename: Shilin N
authors.initials: SN
authors.lastname: Shukla
authors.forename: Pankaj M
authors.initials: PM
authors.lastname: Shah
authors.forename: Prabhudas S
authors.initials: PS
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011379:Prognosis; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases