The Prognostic Significance of Pretreatment Serum CEA Levels in Gastric Cancer: A Meta-Analysis Including 14651 Patients

Background
Carcinoembryonic antigen (CEA) is commonly used as a serum tumor marker in clinical practice; however, its prognostic value for gastric cancer patients remains uncertain. This meta-analysis was performed to assess the prognostic value of CEA and investigate CEA as a tumor marker.
Methods
PubMed, EMBASE and other databases were searched for potentially eligible studies. Forty-one studies reporting the prognostic effect of pretreatment serum CEA expression in gastric cancer patients were selected. Data on 14651 eligible patients were retrieved for the meta-analysis. Based on the data extracted from the available literature, the hazard ratio (HR) and 95% confidence interval (CI) for an adverse prognosis were estimated for gastric cancer patients with elevated pretreatment serum levels of CEA (CEA+) relative to patients with normal pretreatment CEA levels (CEA-).
Results
The CEA+ patients had a significantly poorer prognosis than the CEA- patients in terms of overall survival (OS: HR 1.716, 95% CI 1.594 - 1.848, P< 0.001), disease-specific survival (DSS: HR 1.940, 95% CI 1.563 - 2.408, P< 0.001), and disease-free survival (DFS: HR 2.275, 95% CI 1.836 - 2.818, P< 0.001). Publication bias and an influence of different cut-off values were not observed (all P> 0.05). In the pooled analyses of multivariate-adjusted HRs, the results suggested that pretreatment serum CEA may be an independent prognostic factor in gastric cancer (OS: HR 1.681, 95% CI 1.425 - 1.982; DSS: HR 1.900, 95% CI 1.441 - 2.505; DFS: HR 2.579, 95% CI 1.935 - 3.436).
Conclusion/Significance
The meta-analysis based on the available literature supported the association of elevated pretreatment serum CEA levels with a poor prognosis for gastric cancer and a nearly doubled risk of mortality in gastric cancer patients. CEA may be an independent prognostic factor for gastric cancer patients and may aid in determining appropriate treatment which may preferentially benefit the CEA+ patients.

研究背景
癌胚抗原（CEA）是临床实践中常用的血清肿瘤标志物，但其用于胃癌患者的预后评估价值仍不明确。本荟萃分析旨在评估CEA的预后价值，并探讨其作为肿瘤标志物的应用潜力。

研究方法
通过检索PubMed、EMBASE等数据库，筛选符合纳入标准的潜在研究。最终纳入41项针对胃癌患者治疗前血清CEA表达水平与预后关联的研究，共提取14651例符合标准的患者数据用于本次荟萃分析。基于公开文献中提取的数据，本研究对比了治疗前血清CEA水平升高的胃癌患者（CEA+组）与治疗前CEA水平正常的患者（CEA-组）的不良预后风险，估算得到风险比（HR）及95%置信区间（CI）。

研究结果
与CEA-组患者相比，CEA+组患者的总生存期（OS：HR=1.716，95%CI=1.594~1.848，P<0.001）、疾病特异性生存期（DSS：HR=1.940，95%CI=1.563~2.408，P<0.001）及无病生存期（DFS：HR=2.275，95%CI=1.836~2.818，P<0.001）均显著更差。未观察到发表偏倚及不同截断值带来的影响（所有P值均>0.05）。在对多变量校正后的风险比进行合并分析后，结果显示治疗前血清CEA水平可作为胃癌的独立预后因素（OS：HR=1.681，95%CI=1.425~1.982；DSS：HR=1.900，95%CI=1.441~2.505；DFS：HR=2.579，95%CI=1.935~3.436）。

结论与意义
本基于公开文献的荟萃分析证实，胃癌患者治疗前血清CEA水平升高与不良预后相关，患者的死亡风险提升近一倍。CEA可作为胃癌患者的独立预后因素，有助于筛选适合的治疗方案，从而使CEA+患者获得更具针对性的临床获益。