Tumor-associated trypsin inhibitor (TATI) and tumor-associated trypsin-2 (TAT-2) predict outcomes in gastric cancer

Authors

  • Aaro Kasurinen Translational Cancer Medicine Research Program, University of Helsinki, Helsinki, Finland
  • Alli Laitinen Translational Cancer Medicine Research Program, University of Helsinki, Helsinki, Finland;  Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • Arto Kokkola Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • Ulf-Håkan Stenman Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • Camilla Böckelman Translational Cancer Medicine Research Program, University of Helsinki, Helsinki, Finland;  Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • Caj Haglund Translational Cancer Medicine Research Program, University of Helsinki, Helsinki, Finland;  Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

DOI:

https://doi.org/10.1080/0284186X.2020.1733655

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.

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Published

2020-06-02

How to Cite

Kasurinen, A., Laitinen, A., Kokkola, A., Stenman, U.-H., Böckelman, C., & Haglund, C. (2020). Tumor-associated trypsin inhibitor (TATI) and tumor-associated trypsin-2 (TAT-2) predict outcomes in gastric cancer. Acta Oncologica, 59(6), 681–688. https://doi.org/10.1080/0284186X.2020.1733655

Issue

Vol. 59 No. 6 (2020): Acta Oncologica

Section

Articles