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. 2010 Sep 17:10:498.
doi: 10.1186/1471-2407-10-498.

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

Alexander Gaber  1 , Björn Nodin, Kristina Hotakainen, Elise Nilsson, Ulf-Håkan Stenman, Anders Bjartell, Helgi Birgisson, Karin Jirström
Affiliations

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

Alexander Gaber et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
ROC curve analysis. ROC curve analysis calculated with the use of survival data (OS), showing AUC on s-TATI compared to s-CEA in all patients (A), curatively treated patients (B). Cut-off based on the point farthest to the northwest (black arrow) extracted from ROC curves data table (data table not shown).
Figure 2
Figure 2
Distribution of s-TATI according to disease stage. Box plots displaying s-TATI distribution in TNM Stage and subcategories. Boxes show 25th, 50th, 75th percentiles, whiskers show 5th and 95th percentile. Outliers are represented with circles while black dots represent extreme outliers. Distribution of s-TATI according to TNM stage (A), tumour stage (B), nodal stage (C) and metastatic stage (D). Kruskal Wallis test was used for statistical analysis.
Figure 3
Figure 3
Prognostic value of s-TATI in all patients. Kaplan Meier estimates of disease free survival and overall survival in strata of s-TATI levels according to the cut-off derived from the ROC analysis (A, C) and quartiles (B, D).
Figure 4
Figure 4
Prognostic impact of s-TATI in Stage II and Stage III disease. Kaplan Meier estimates of disease free survival according to high and low s-TATI levels derived from ROC-analysis in Stage II (A) and Stage III patients (B), and overall survival in Stage II (C) and Stage III patients (D), respectively.
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References

    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108. doi: 10.3322/canjclin.55.2.74. - DOI - PubMed
    1. Iqbal S, Stoehlmacher J, Lenz HJ. Tailored chemotherapy for colorectal cancer: a new approach to therapy. Cancer Invest. 2004;22(5):762–773. doi: 10.1081/CNV-200032774. - DOI - PubMed
    1. Gaber A, Johansson M, Stenman UH, Hotakainen K, Ponten F, Glimelius B, Bjartell A, Jirstrom K, Birgisson H. High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer. British journal of cancer. 2009;100(10):1540–1548. doi: 10.1038/sj.bjc.6605047. - DOI - PMC - PubMed
    1. Gouyer V, Fontaine D, Dumont P, de Wever O, Fontayne-Devaud H, Leteurtre E, Truant S, Delacour D, Drobecq H, Kerckaert JP. et al.Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells. Oncogene. 2008;27(29):4024–4033. doi: 10.1038/onc.2008.42. - DOI - PubMed
    1. Venesmaa P, Lehtovirta P, Stenman UH, Leminen A, Forss M, Ylikorkala O. Tumour-associated trypsin inhibitor (TATI): comparison with CA125 as a preoperative prognostic indicator in advanced ovarian cancer. British journal of cancer. 1994;70(6):1188–1190. - PMC - PubMed

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