title: Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients.
abstract: BACKGROUND
  There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC) management. In a previous study, we found that high tumour tissue expression of tumour-associated trypsin inhibitor (TATI) correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of serum TATI (s-TATI) in CRC. We further assessed the prognostic value of carcino-embryonic antigen in serum (s-CEA) and the interrelationship between s-TATI and TATI in tissue (t-TATI).
  
  
  METHODS
  Using an immunofluorometric assay, s-TATI levels were analysed in 334 preoperatively collected serum samples from patients with CRC. Spearman's Rho and Chi-square test were used for analysis of correlations between s-TATI and clinicopathological parameters, s-CEA and t-TATI. Kaplan-Meier analysis and Cox uni- and multivariate regression analysis were used to estimate disease free survival (DFS) and overall survival (OS) according to quartiles of s-TATI and cut-offs derived from ROC-analysis of s-TATI and s-CEA.
  
  
  RESULTS
  Increased levels of s-TATI were associated with a reduced DFS (HR = 2.00; 95% CI 1.40-2.84, P < 0.001) and OS (HR = 2.40; 95% CI 1.74-3.33, P < 0.001). (HR = 2.89; 95% CI 1.96-4.25). This association remained significant in multivariate analysis. The association for OS remained significant in multivariate analysis (HR = 1.51; 95% CI 1.03-2.22, P = 0.034 for DFS and HR = 1.78; 95% CI 1.25-2.53, P = 0.001 for OS). There was no significant association between s-TATI and t-TATI. The prognostic value of s-CEA was also evident, but somewhat weaker than for s-TATI.
  
  
  CONCLUSIONS
  High preoperative s-TATI levels predict a poor prognosis in patients with CRC, and the prognostic value is independent of established prognostic parameters and t-TATI expression. These data suggest that s-TATI might be a useful marker for prognostic stratification in CRC.
authors.affiliation: Department of Laboratory Medicine, Lund University, Skåne University Hospital, Center for Molecular Pathology, Malmö, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gaber
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.forename: Kristina
authors.initials: K
authors.lastname: Hotakainen
authors.forename: Elise
authors.initials: E
authors.lastname: Nilsson
authors.forename: Ulf-Håkan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Helgi
authors.initials: H
authors.lastname: Birgisson
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D015996:Survival Rate; D046888:Tissue Array Analysis; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D014359:Trypsin Inhibitor, Kazal Pancreatic