Nielsen Hans J, Christensen Ib J, Brünner Nils
Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
Scand J Gastroenterol. 2010;45(2):200-7. doi: 10.3109/00365520903429406.
The introduction of stage-independent prognostic markers may play a significant role in future selection for adjuvant treatment for early-stage colorectal cancer (CRC). The purpose of this study was to assess the combination of preoperative serum carcinoembryonic antigen (CEA) and plasma tissue inhibitor of metalloproteinases (TIMP)-1 as a prognostic index in patients with primary, curatively resected CRC.
Blood samples were collected before surgery from 422 patients with CRC stage I-III (Dukes' stage A-C). CEA was determined in serum by a routine analysis and TIMP-1 was determined in plasma using a validated in-house enzyme-linked immunosorbent assay. Disease-free survival (DFS) was registered and its associations with serum CEA and plasma TIMP-1 levels were studied using a Cox multivariate model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for DFS were calculated.
An event was recorded in 186 patients: 75 had local recurrence, 75 had distant metastases, 28 had both local recurrence and distant metastases, and 36 died from their cancer without a registered recurrence. Scoring CEA and TIMP-1 as continuous variables on a logarithmic scale, serum CEA and plasma TIMP-1 were statistically significant in a multivariate analysis with HR = 1.1 (95% CI 1.0-1.2) and HR = 1.5 (95% CI 1.1-2.0), respectively. The two serological markers could be combined to form a prognostic index adjusted for baseline variables. This index showed a 51% increase in HR for a given CEA level if the TIMP-1 level was doubled.
Preoperative serum CEA and plasma TIMP-1 levels are independent predictors of DFS in patients with primary resectable CRC. In combination these two proteins could form an index for the assessment of risk of disease recurrence in early-stage CRC.
引入不依赖分期的预后标志物可能在未来早期结直肠癌（CRC）辅助治疗的选择中发挥重要作用。本研究的目的是评估术前血清癌胚抗原（CEA）和血浆金属蛋白酶组织抑制剂（TIMP）-1的联合检测作为原发性、根治性切除CRC患者的预后指标。
对422例I-III期（Dukes分期A-C）CRC患者在手术前采集血样。通过常规分析测定血清中的CEA，并使用经过验证的内部酶联免疫吸附测定法测定血浆中的TIMP-1。记录无病生存期（DFS），并使用Cox多变量模型研究其与血清CEA和血浆TIMP-1水平的相关性。计算DFS的风险比（HRs）和95%置信区间（95% CIs）。
186例患者出现事件：75例局部复发，75例远处转移，28例既有局部复发又有远处转移，36例死于癌症但未记录到复发。将CEA和TIMP-1作为对数尺度上的连续变量进行评分，在多变量分析中，血清CEA和血浆TIMP-1具有统计学意义，HR分别为1.1（95% CI 1.0-1.2）和1.5（95% CI 1.1-2.0）。这两种血清学标志物可以结合形成一个针对基线变量进行调整的预后指标。如果TIMP-1水平翻倍，对于给定的CEA水平，该指标显示HR增加51%。
术前血清CEA和血浆TIMP-1水平是原发性可切除CRC患者DFS的独立预测指标。这两种蛋白质联合可形成一个用于评估早期CRC疾病复发风险的指标。
