术前血清癌胚抗原质量浓度对非小细胞肺癌患者预后作用的Meta分析

doi:10.3969/j.issn.1006-7795.2014.06.006

摘要/Abstract

摘要：

目的分析术前血清癌胚抗原(carcinoembryonic antigen,CEA)质量浓度对非小细胞肺癌(non-small cell lung cancer,NSCLC)的预后价值。方法检索截至2014年6月1日数据库相关研究文献,针对术前血清CEA质量浓度与NSCLC患者生存关系进行定量评估并符合条件的文献行meta分析,汇总生存数据并行定量分析。结果共有16个研究(n=4 296)评估NSCLC患者中术前CEA质量浓度与患者的生存。组合风险比(hazard ratio,HR)提示NSCLC患者中,术前血清CEA过表达与总生存期不良预后相关(HR=2.28,95% CI:2.2~2.31)。同时对于病理分期为Ⅰ期的NSCLC患者,风险比是1.98(95%CI:1.73~2.15)。患者资料进行分层分析后结果显示亚洲和非亚洲患者中显著风险相关。然而,在所有研究中发现存在显著的异质性。结论术前血清CEA的高表达提示NSCLC患者预后不良。

关键词: 癌胚抗原, 预后, 肺癌, 非小细胞肺癌, 荟萃分析

Abstract:

Objective To explore the prognostic role of preoperative serum carcinoembryonic antigen(CEA) levels in non-small cell lung cancer(NSCLC) patients. Methods Electronic databases updated to June 1, 2014 were searched to find relevant studies. A meta-analysis was made with eligible studies which quantitatively evaluated the relationship between preoperative serum CEA level and survival of patients with NSCLC. Survival data were aggregated and quantitatively analyzed. Results Totally 16 studies(n=4 296 patients) were enrolled. We evaluated the correlation between preoperative serum CEA level and survival in patients with NSCLC. Combined hazard ratios suggested that preoperative serum CEA overexpression was associated with poor prognosis of overall survival(OS)(HR=2.28, 95% CI: 2.24-2.31) in patients. Meanwhile, for p-stage I NSCLC, the HR(95% CI) was 1.98(1.73-2.15). In the stratified analysis by patient source, significant risks were found among Asians and non-Asians. However, significant heterogeneity was observed among all studies. Conclusion In the present meta-analysis, preoperative serum CEA overexpression indicated a poor prognosis for patients with NSCLC.

Key words: carcinoembryonic antigen, prognosis, lung cancer, non-small cell lung cancer, meta-analysis

中图分类号:

刘树库, 王晓彬, 李杰, 曹小庆, 韩毅, 刘志东. 术前血清癌胚抗原质量浓度对非小细胞肺癌患者预后作用的Meta分析[J]. 首都医科大学学报, 2014, 35(6): 705-710.

Liu Shuku, Wang Xiaobin, Li Jie, Cao Xiaoqing, Han Yi, Liu Zhidong. Prognostic significance of preoperative serum carcinoembryonic antigen in non-small cell lung cancer: a Meta-analysis[J]. Journal of Capital Medical University, 2014, 35(6): 705-710.

参考文献

[1] Jemal A, Siegel R, Xu J, et.al. Cancer statistics,2010[J]. CA Cancer J Clin, 2010,60(5):277-300.
[2] Molina J R, Yang P, Cassivi S D, et al. Non-small cell lung cancer: epidemiology, risk factors,treatment, and survivorship[J]. Mayo Clin Proc, 2008,83(5):584-594.
[3] Alberg A J, Ford J G, Samet J M, et al. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines[J]. Chest, 2007,132(3 Suppl):29S-55S.
[4] Paesmans M, Sculier J P, Libert P, et al. Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patient. The European Lung Cancer Working Partys[J]. J Clin Oncol, 1995,13(5):1221-1230.
[5] Donnem T, Bremnes R M, Busund L T, et.al. Gene expression assays as prognostic and predictive markers in early stage non-small cell lung cancer[J]. J Thorac Dis, 2012,4(2):212-213.
[6] Osarogiagbon R U. Predicting survival of patients with resectable non-small cell lung cancer: Beyond TNM[J]. J Thorac Dis, 2012,4(2):214-216.
[7] Hanagiri T, Sugaya M, Takenaka M, et.al. Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer[J]. Lung Cancer, 2011,74(1):112-117.
[8] Gold P, Freedman S O. Specific carcinoembryonic antigens of the human digestive system[J]. J Exp Med, 1965,122(3):467-481.
[9] Okada M, Nishio W, Sakamoto T, et al. Prognostic significance of perioperative serum carcinoembryonic antigen in non-small cell lung cancer: analysis of 1 000 consecutive resections for clinical stage I disease[J]. Ann Thorac Surg, 2004,78(1):216-221.
[10] Lee J H, Chang J H. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments in patients with effusions from primary lung cancer[J]. Chest, 2005,128(4): 2298-2303.
[11] Carcinoembryonic antigen: its role as a marker in the management of cancer. Summary of an NIH ansensus statement[J]. Br Med J(Clin Res Ed), 1981,282(6261):373-375.
[12] Pretreatment evaluation of non-small-cell lung cancer. American Thoracic Society and European respiratory Society[J]. Am J Respir Crit Care Med, 1997,156(1):320-332.
[13] Altman D G. Systematic reviews of evaluations of prognostic variables[J]. BMJ, 2001,323(7306):224-228.
[14] Parmar M K, Torri V, Stewart L. Extracting summary statistics to perform meta analyses of the published literature for survival endpoints[J]. Stat Med, 1998,17(24):2815-2834.
[15] Yusuf S, Peto R, Lewis J, et al. Blockade during and after myocardial infarction: an overview of the randomized trials[J]. Prog Cardiovasc Dis, 1985,27(5):335-371.
[16] DerSimonian R, Laird N. Meta-analysis in clinical trials[J]. Control Clin Trials, 1986,7(3):177-188.
[17] Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test[J]. BMJ, 1997,315(7109):629-634.
[18] Begg C B, Mazumdar M. Operating characteristics of a rank correlation test for publication bias[J]. Biometrics, 1994,50(4):1088-1101.
[19] Tomita M, Shimizu T, Ayabe T, et al. Maximum SUV on positron emission tomography and serum CEA level as prognostic factors after curative resection for non-small cell lung cancer[J]. Asia Pac J Clin Oncol, 2012,8(3):244-247.
[20] Tomita M, Shimizu T, Ayabe T, et al. Prognostic significance of tumour marker index based on preoperative CEA and CYFRA 21-1 in non-small cell lung cancer[J]. Anticancer Res, 2010,30(7):3099-3102.
[21] Blankenburg F, Hatz R, Nagel D, et al. Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer: external validation of a prognostic score[J]. Tumour Biol, 2008,29(4):272-277.
[22] Fukai R, Sakao Y, Sakuraba M, et al. The prognostic value of carcinoem bryonic antigen in T1N1M0 and T2N1M0 non-small cell carcinoma of the lung[J]. Eur J Cardiothorac Surg, 2007,32(3):440-444.
[23] Matsuoka K, Sumitomo S, Nakashima N, et al. Prognostic value of carcinoembryonic antigen and CYFRA21-1 in patients with pathological stage I non-small cell lung cancer[J]. Eur J Cardiothorac Surg, 2007,32(3):435-439.
[24] Hsu W H, Huang C S, Hsu H S, et al. Preoperative serum carcinoembryonic antigen level is a prognostic factor in women with early non-small-cell lung cancer[J]. Ann Thorac Surg, 2007,83(2):419-424.
[25] Tsuchiya T, Akamine S, Muraoka M, et al. Stage IA non-small cell lung cancer: vessel invasion is a poor prognostic factor and a new target of adjuvant chemotherapy[J]. Lung Cancer, 2007,56(3):341-348.
[26] Tomita M, Matsuzaki Y, Shimizu T, et al. Relationship between serum carcinoembryonic antigen level and T status in non-small cell lung cancer[J]. Anticancer Res, 2006,26(5B):3845-3848.
[27] Muley T, Dienemann H, Ebert W, et al. CYFRA 21-1 and CEA are independent prognostic factors in 153 operated stage I NSCLC patients[J]. Anticancer Res, 2004,24(3b):1953-1956.
[28] Niizeki H, Morikawa T, Okushiba S, et al. Survival and prognostic factors in resected cN2-pN0 non-small cell lung cancer[J]. Ann Thorac Cardiovasc Surg, 2004,10(1):9-13.
[29] Okada M, Sakamoto T, Nishio W, et al. Characteristics and prognosis of patients after resection of non small cell lung carcinoma measuring 2cm or less in greatest dimension[J]. Cancer, 2003,98(3):535-541.
[30] Sawabata N, Ohta M, Takeda S, et al. Serum carcinoembryonic antigen level in surgically resected clinical stage I patients with non-small cell lung cancer[J]. Ann Thorac Surg, 2002,74(1):174-179.
[31] Suzuki K, Nagai K, Yoshida J, et al. The prognosis of surgically resected N2 non-small cell lung cancer: the importance of clinical N status[J]. J Thorac Cardiovasc Surg, 1999,118(1):145-153.
[32] Graziano S L, Tatum A H, Newman N B. The prognostic significance of neuroendocrine markers and carcinoembryonic antigen in patients with resected stage I and II non-small cell lung cancer[J]. Cancer Res, 1994,54(11):2908-2913.
[33] Steels E, Paesmans M, Berghmans T, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis[J]. Eur Respir J, 2001,18(4):705-719.
[34] Meert A P, Paesmans M, Martin B, et al. The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis[J]. Br J Cancer, 2002,87(7):694-701.
[35] Meert A P, Martin B, Paesmans M, et al. The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature[J]. Br J Cancer, 2003,89(6):959-965.
[36] Martin B, Paesmans M, Berghmans T, et al. Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis[J]. Br J Cancer, 2003,89(1):55-64.
[37] Martin B, Paesmans M, Mascaux C, et al. Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis[J]. Br J Cancer, 2004,91(12):2018-2025.
[38] Mascaux C, Iannino N, Martin B, et al. The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis[J]. Br J Cancer, 2005,92(1):131-139.
[39] Meert A P, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis[J]. Eur Respir J, 2002,20(4):975-981.
[40] Nakamura H, Kawasaki N, Taguchi M, et al. Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: a meta-analysis[J]. Thorax, 2006,61(2):140-145.
[41] Fan J, Wang L, Jiang G N, et al. The role of survivin on overall survival of non-small cell lung cancer, a meta-analysis of published literatures[J]. Lung Cancer, 2008,61(1):91-96.
[42] 周明术,邓述凯.肿瘤分子标志联合检测对胸腔积液鉴别诊断价值分析[J].中华肿瘤防治杂志,2013,20(10):772-774.
[43] 鲁立军,谢云亭,许凝.术中胸膜腔冲洗液细胞学及CEA检测对NSCLC胸膜腔微转移预测价值分析[J].中华肿瘤防治杂志,2012,19(21):1643-1646.
[44] Begg C B, Berlin J A. Publication bias nd dissemination of clinical research data[J]. J Natl Cancer Inst, 1989,81(2):107-115.