title: Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia.
  
  
  OBJECTIVE
  To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels.
  
  
  METHODS
  We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia.
  
  
  RESULTS
  Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%).
  
  
  CONCLUSIONS
  Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers.
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain. Electronic address: antozeben@gmail.com.
authors.forename: Antonio Z
authors.initials: AZ
authors.lastname: Gimeno-García
authors.affiliation: Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Triñanes
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain; La Laguna University, Tenerife, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Quintero
authors.affiliation: Pathology Department, La Laguna University, Tenerife, Spain; La Laguna University, Tenerife, Spain; Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salido
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Nicolás-Pérez
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Zaida
authors.initials: Z
authors.lastname: Adrián-de-Ganzo
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Onofre
authors.initials: O
authors.lastname: Alarcón-Fernández
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Abrante
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Carrillo
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ramos
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Alonso
authors.affiliation: Gastroenterology Department, La Laguna University, Tenerife, Spain; Pathology Department, La Laguna University, Tenerife, Spain; La Laguna University, Tenerife, Spain; Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ortega
authors.affiliation: Research Unit, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D000236:Adenoma / Q000097:blood / Q000737:chemistry / Q000473:pathology; D018256:Adenomatous Polyps / Q000097:blood / Q000737:chemistry / Q000473:pathology; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood* / Q000235:genetics; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood* / Q000737:chemistry / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Adenoma avanzado; Advanced adenoma; Biomarcadores en plasma; Colorectal cancer; Cáncer colorrectal; Gelatin zymography; Matrix metalloproteinases; Metaloproteinasas; Plasma biomarker; Zimografía con gelatina