title: A case-control study of pre-operative levels of serum neutrophil gelatinase-associated lipocalin and other potential inflammatory markers in colorectal cancer.
abstract: BACKGROUND
  Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP).
  
  
  METHODS
  The AGARIC multicenter case-control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n=224) or for benign causes (n=252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured.
  
  
  RESULTS
  Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p<0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR=2.44 (95% CI : 1.34-4.45, p=0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case-control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p=0.028) but this association was reduced after adjustment for CRP (p=0.11).
  
  
  CONCLUSIONS
  Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.
authors.affiliation: Inserm UMR 866, Faculté de médecine de Dijon, Dijon 21079-F, France. laurence.duvillard@chu-dijon.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortega-Deballon
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Bourredjem
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Scherrer
authors.forename: Georges
authors.initials: G
authors.lastname: Mantion
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Delhorme
authors.forename: Sophie
authors.initials: S
authors.lastname: Deguelte-Lardière
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Petit
authors.forename: Claire
authors.initials: C
authors.lastname: Bonithon-Kopp
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D057234:Preoperative Period; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012372:ROC Curve; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D047368:Tumor Burden
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9