Translational Cancer Medicine Research Program, University of Helsinki, Helsinki, Finland.
Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Acta Oncol. 2020 Jun;59(6):681-688. doi: 10.1080/0284186X.2020.1733655. Epub 2020 Mar 3.
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). 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. 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; = .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; < .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; < .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 ( = .037). 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.
肿瘤相关胰蛋白酶抑制剂（TATI）限制丝氨酸蛋白酶，促进几种癌症的癌变，并作为急性期反应物发挥作用。肿瘤相关胰蛋白酶-2（TAT-2）是 TATI 的靶酶蛋白酶，可以通过促进细胞外基质降解来增强侵袭。在这里，我们旨在研究血清 TATI 和 TAT-2 水平，包括 TAT-2/TATI 比值，作为胃癌的预后和诊断生物标志物。我们将结果与血浆 C-反应蛋白（CRP）水平进行了比较。我们选择了 2000 年至 2009 年间在芬兰赫尔辛基大学医院接受胃腺癌手术的 240 名个体。我们使用单克隆抗体的时间分辨免疫荧光测定法测定术前血清 TAT-2、TATI 和血浆 CRP 水平。与良性对照组相比，胃癌患者的血清 TAT-2 水平较高[中位数 8.68ng/ml；四分位距（IQR）5.93-13.2]（中位数 5.41ng/ml；IQR 4.12-11.8； = .005）。高水平血清 TAT-2 的患者 5 年生存率为 22.9%（95%CI 11.7-34.1），而低水平组为 52.2%（95%CI 44.6-59.8； < .001）。高水平血清 TATI 的患者 5 年生存率为 30.6%（95%CI 20.4-40.8），而低水平组为 52.9%（95%CI 44.7-61.1； < .001）。多变量生存分析中，血清 TATI 水平仍然具有显著意义（危险比 2.01；95%CI 1.32-3.07）。升高的血浆 CRP 水平与高水平的血清 TATI 相关（ = .037）。这项研究首次表明，高水平的血清 TAT-2 可能作为胃癌的预后生物标志物发挥作用，并且与对照组相比，TAT-2 水平可能升高。此外，我们表明，高水平血清 TATI 的胃癌患者预后更差。这些生物标志物是预后因素，尤其是在患有转移性或局部晚期疾病的患者中。
