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Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients.

Gaber, Alexander LU ; Nodin, Björn; Hotakainen, Kristina; Nilsson, Elise LU ; Stenman, Ulf-Håkan; Bjartell, Anders LU ; Birgisson, Helgi and Jirström, Karin LU (2010) In BMC Cancer 10(1).
Abstract
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
BMC Cancer
volume
10
issue
1
publisher
BioMed Central
external identifiers
  • WOS:000282723200002
  • PMID:20849596
  • Scopus:79952199361
ISSN
1471-2407
DOI
10.1186/1471-2407-10-498
language
English
LU publication?
yes
id
54c55a40-aec1-4d99-bef7-d01631a93fb4 (old id 1688088)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20849596?dopt=Abstract
date added to LUP
2010-10-05 10:21:05
date last changed
2016-12-04 04:39:50
@misc{54c55a40-aec1-4d99-bef7-d01631a93fb4,
  abstract     = {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 &lt; 0.001) and OS (HR = 2.40; 95% CI 1.74-3.33, P &lt; 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.},
  author       = {Gaber, Alexander and Nodin, Björn and Hotakainen, Kristina and Nilsson, Elise and Stenman, Ulf-Håkan and Bjartell, Anders and Birgisson, Helgi and Jirström, Karin},
  issn         = {1471-2407},
  language     = {eng},
  number       = {1},
  publisher    = {ARRAY(0xb936f28)},
  series       = {BMC Cancer},
  title        = {Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients.},
  url          = {http://dx.doi.org/10.1186/1471-2407-10-498},
  volume       = {10},
  year         = {2010},
}