title: Evaluation of alpha 1-antitrypsin and the levels of mRNA expression of matrix metalloproteinase 7, urokinase type plasminogen activator receptor and COX-2 for the diagnosis of colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool.
  
  
  OBJECTIVE
  Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC.
  
  
  METHODS
  In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7), urokinase-type plasminogen activator receptor (uPAR), urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF), cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2), and CD44) and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA) and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results.
  
  
  RESULTS
  Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79 ± 0.25 in the CRC group vs 1.27 ± 0.25 in the control group, P<0.0005). The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79-0.96). The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81) and tetranectin (0.80), COX-2 (0.78), uPAR (0.78) and carbonic anhydrase (0.77). The markers which identified early stage CRC (Stages I and II) were alpha 1-antitrypsin, uPAR, COX-2 and MMP7.
  
  
  CONCLUSIONS
  Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages.
authors.affiliation: Department of Gastroenterology, Donostia Hospital-Biodonostia Institute, University of Basque Country, UPV/EHU, Centro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas, San Sebastián, Spain. medik@telefonica.net
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.forename: Cristina
authors.initials: C
authors.lastname: Sarasqueta
authors.forename: Angel
authors.initials: A
authors.lastname: Cosme
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hijona
authors.forename: José M
authors.initials: JM
authors.lastname: Enríquez-Navascués
authors.forename: Carlos
authors.initials: C
authors.lastname: Placer
authors.forename: Eloisa
authors.initials: E
authors.lastname: Villarreal
authors.forename: Marta
authors.initials: M
authors.lastname: Herreros-Villanueva
authors.forename: María D
authors.initials: MD
authors.lastname: Giraldez
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D003113:Colonoscopy / Q000379:methods; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D000515:alpha 1-Antitrypsin / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; C524898:PLAUR protein, human; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; D000515:alpha 1-Antitrypsin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7