Department of Surgery, Uppsala University, 75185 Uppsala, Sweden.
Eur J Cancer. 2010 Dec;46(18):3323-31. doi: 10.1016/j.ejca.2010.06.009. Epub 2010 Jul 7.
Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC.
During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms.
High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels.
This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.
先前的研究表明，血浆组织金属蛋白酶抑制剂-1（TIMP-1）是结直肠癌（CRC）患者无分期相关的预后标志物。本研究旨在验证血浆 TIMP-1 和血清癌胚抗原（CEA）水平是否可作为 CRC 患者独立的基于人群队列的预后指标。
2000-2003 年，采集了 322 例原发性 CRC 患者术前的血浆和血清标本。采用已验证的 ELISA 平台检测 TIMP-1 和 CEA 水平。
高 TIMP-1 和 CEA 水平均与总体生存（OS）不良相关；TIMP-1（风险比（HR）2.1；95%置信区间（CI）1.6-2.7）和 CEA（HR 1.2；95%CI 1.1-1.3），以及无病生存（DFS）；TIMP-1（HR 2.0；95%CI：1.5-2.6）和 CEA（HR 1.2；95%CI：1.1-1.4）。在 II 期和 III 期的分层分析中，TIMP-1 水平与 II 期和 III 期的 OS 和 DFS 显著相关，而 CEA 无相关性。OS 的多变量分析，包括 TIMP-1 和 CEA 水平以及临床病理基线变量，显示 TIMP-1（HR 1.8；95%CI 1.3-2.4）而不是 CEA 水平与 OS 显著相关。
这项独立的前瞻性验证研究证实了术前血浆 TIMP-1 水平与 CRC 患者生存之间存在显著相关性：TIMP-1 提供的预后信息比 CEA 更具优势。因此，这项研究使血浆 TIMP-1 在其作为 CRC 患者的临床预后标志物的应用方面达到了更高的证据水平。
