Department of Laboratory Medicine, Lund University, Skåne University Hospital, Center for Molecular Pathology, Malmö, Sweden.
BMC Cancer. 2010 Sep 17;10:498. doi: 10.1186/1471-2407-10-498.
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).
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.
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.
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.
在结直肠癌（CRC）管理中，可靠的预后和反应预测生物标志物数量不足。在之前的研究中，我们发现肿瘤组织中肿瘤相关胰蛋白酶抑制剂（TATI）的高表达与CRC 的肝转移和预后不良相关。本研究旨在探讨CRC 患者血清 TATI（s-TATI）的预后价值。我们进一步评估了血清癌胚抗原（s-CEA）的预后价值以及 s-TATI 与组织 TATI（t-TATI）之间的相互关系。
使用免疫荧光测定法分析了 334 例术前收集的 CRC 患者血清样本中的 s-TATI 水平。采用 Spearman's Rho 和 Chi-square 检验分析 s-TATI 与临床病理参数、s-CEA 和 t-TATI 之间的相关性。根据 s-TATI 的四分位数和 s-TATI 和 s-CEA 的 ROC 分析得出的截断值，采用 Kaplan-Meier 分析和 Cox 单因素和多因素回归分析估计无病生存期（DFS）和总生存期（OS）。
s-TATI 水平升高与 DFS（HR = 2.00；95%CI 1.40-2.84，P < 0.001）和 OS（HR = 2.40；95%CI 1.74-3.33，P < 0.001）降低相关。（HR = 2.89；95%CI 1.96-4.25）。这一关联在多因素分析中仍然显著。OS 的相关性在多因素分析中仍然显著（DFS 的 HR = 1.51；95%CI 1.03-2.22，P = 0.034，OS 的 HR = 1.78；95%CI 1.25-2.53，P = 0.001）。s-TATI 与 t-TATI 之间没有显著相关性。s-CEA 的预后价值也很明显，但比 s-TATI 稍弱。
术前 s-TATI 水平高可预测 CRC 患者预后不良，其预后价值独立于既定的预后参数和 t-TATI 表达。这些数据表明，s-TATI 可能是 CRC 预后分层的有用标志物。
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