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- Title
Tumor-associated trypsin inhibitor (TATI) and tumor-associated trypsin-2 (TAT-2) predict outcomes in gastric cancer.
- Authors
Kasurinen, Aaro; Laitinen, Alli; Kokkola, Arto; Stenman, Ulf-Håkan; Böckelman, Camilla; Haglund, Caj
- Abstract
Introduction: Tumor-associated trypsin inhibitor (TATI) limits serine proteases, promotes carcinogenesis in several cancers and functions as an acute-phase reactant. Tumor-associated trypsin-2 (TAT-2), a proteolytic target enzyme for TATI, can enhance invasion by promoting extracellular matrix degradation. Here, we aimed to study serum TATI and TAT-2 levels, including the TAT-2/TATI ratio, as prognostic and diagnostic biomarkers in gastric cancer. We compared the results with the plasma level of C-reactive protein (CRP). Material and Methods: We selected 240 individuals operated on for gastric adenocarcinoma at the Helsinki University Hospital, Finland, between 2000 and 2009. We determined the preoperative serum TAT-2, TATI and plasma CRP levels using time-resolved immunofluorometric assays using monoclonal antibodies. Results: The medium serum TAT-2 level was higher among gastric cancer patients [8.68 ng/ml; interquartile range (IQR) 5.93–13.2] than among benign controls (median 5.41 ng/ml; IQR 4.12–11.8; p =.005). Five-year survival among patients with a high serum TAT-2 was 22.9% [95% confidence interval (CI) 11.7–34.1], compared to 52.2% (95% CI 44.6–59.8; p <.001) among those with a low level. The five-year survival among patients with a high serum TATI was 30.6% (95% CI 20.4–40.8), compared to 52.9% (95% CI 44.7–61.1; p <.001) among those with a low level. The serum TATI level remained significant in the multivariable survival analysis (hazard ratio 2.01; 95% CI 1.32–3.07). An elevated plasma CRP level associated with a high serum TATI level (p =.037). Conclusions: This study shows for the first time that a high serum TAT-2 may function as a prognostic biomarker in gastric cancer and that TAT-2 levels may be elevated compared to controls. Additionally, we show that the prognosis is worse among gastric cancer patients with a high serum TATI. These biomarkers serve as prognostic factors particularly among patients with a metastatic or a locally advanced disease.
- Subjects
FINLAND; ACADEMIC medical centers; ACUTE phase proteins; C-reactive protein; COMPARATIVE studies; CONFIDENCE intervals; DIGESTIVE organ surgery; MONOCLONAL antibodies; MULTIVARIATE analysis; STOMACH tumors; SURVIVAL; TRYPSIN; TUMOR markers; TREATMENT effectiveness; PREOPERATIVE period; FLUOROIMMUNOASSAY; ODDS ratio
- Publication
Acta Oncologica, 2020, Vol 59, Issue 6, p681
- ISSN
0284-186X
- Publication type
Article
- DOI
10.1080/0284186X.2020.1733655