Dataset Information

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.

SUBMITTER: Gaber A

PROVIDER: S-EPMC2946315 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Gaber Alexander A Nodin Björn B Hotakainen Kristina K Nilsson Elise E Stenman Ulf-Håkan UH Bjartell Anders A Birgisson Helgi H Jirström Karin K

BMC cancer 20100917

<h4>Background</h4>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 ...[more]

PMID: 20849596

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Project description:Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, -?9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation.We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998-2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test.Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17-2.52, P?=?0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23-2.64, P?=?0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33-0.98, P?=?0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS?=?0.229, P?<?0.001), and TIMP-1 (rS?=?0.280, P?<?0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10-2.53, P?=?0.017) and TIMP-1 (HR 1.59, 95% CI 1.05-2.42, P?=?0.029) were prognostic factors.MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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