血清肿瘤相关胰蛋白酶抑制剂水平升高可独立预测结直肠癌患者预后不良。
Increased serum levels of tumour-associated trypsin inhibitor independently predict a poor prognosis in colorectal cancer patients.
机构信息
Department of Laboratory Medicine, Lund University, Skåne University Hospital, Center for Molecular Pathology, Malmö, Sweden.
出版信息
BMC Cancer. 2010 Sep 17;10:498. doi: 10.1186/1471-2407-10-498.
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.
背景
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。
方法
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）。
结果
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。
结论
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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