手术前后血清CEA和CYFRA21-1水平的变化有助于预测非小细胞肺癌患者的预后
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摘要
背景与目的血清癌胚抗原(carcinoembryonic antigen,CEA)和细胞角蛋白19的可溶性片段(soluble fragment of cytokeratin-19,CYFRA21-1)系非小细胞肺癌(non-small cell lung cancer,NSCLC)患者术前检查重要的肿瘤标志物(tumor markers,TMs),但其对NSCLC患者术后的预后作用尚存争议。本研究旨在探讨血清CEA和CYFRA21-1在手术治疗后的NSCLC患者预后中的临床价值。方法回顾性总结175例经手术并辅以化疗的NSCLC患者的临床资料及随访情况,依据CEA、CYFRA21-1水平进行分组,用Kaplan-Meier法对各组进行生存分析。用Cox比例风险回归模型分析影响NSCLC患者术后预后的因素。结果术前CEA、CYFRA21-1升高组的患者总生存时间(overall survival,OS)少于术前正常组的患者,术前CYFRA21-1升高组差异有统计学意义(P=0.001)。与术前术后CEA、CYFRA21-1均正常等组的患者OS比较,术前术后CEA、CYFRA21-1均升高组的患者OS最短,两组差异均有统计学意义(P<0.05)。与CEA联合CYFRA21-1术前术后均正常等组的患者OS比较,CEA联合CYFRA21-1术前术后均升高组的患者OS最短,差异有统计学意义(P<0.001)。CEACYFRA21-1(HHHH)、CEACYFRA21-1(NNHH)、CYFRA21-1(HH)、CEA(HH)、男性是判断预后的独立危险因素(P<0.05)。结论血清CEA或CYFRA21-1在手术前及术后均高于正常,尤其是两者联合在手术前及术后均升高的NSCLC患者预后不良。手术前后血清CEA、CYFRA21-1的检测有助于NSCLC患者术后预后的判断。
Background and objective Serum carcinoembryonic antigen(CEA) and the soluble fragment of cytokeratin 19(CYFRA21-1) are important tumor markers(TMs) in the preoperative examination of patients with non-small cell lung cancer(NSCLC). However, the prognostic role of these markers in NSCLC patients remains controversial. The aim of the study was to investigate the clinical significance of serum CEA variances and CYFRA21-1 levels for the prognosis of NSCLC patients following surgery. Methods This retrospective study investigated the clinical records and follow-up sessions of 175 patients with NSCLC who accepted surgery and adjuvant chemotherapy. Patients were subdivided into groups based on serum CEA and CYFRA21-1 levels. Survival analysis was conducted using Kaplan-Meier method for each group. The prognostic factor was evaluated using Cox proportional hazards model. Results The overall survival(OS) of patients with high preoperative CEA or CYFRA21-1 levels was lower than that of patients with normal preoperative CEA or CYFRA21-1 levels. The OS displayed a significant difference(P=0.001) between groups with high and normal preoperative CYFRA21-1. Compared with groups exhibiting normal preoperative and postoperative levels of CEA or CYFRA21-1, the OS was shorter for groups with high preoperative and postoperative levels of CEA or CYFRA21-1. The difference of the paired groups was significant(P<0.05). Compared with the groups with normal preoperative and postoperative levels of CEA and CYFRA21-1, the OS was lower for the groups with high preoperative and postoperative levels of CEA and CYFRA21-1, which indicated a significant difference(P<0.001). The CEACYFRA211(HHHH), CEACYFRA211(NNHH), CYFRA21-1(HH), CEA(HH), and male genderwere identified as independent prognostic factors(P<0.05). Conclusion This study suggested that the prognosis of NSCLC patients was not significantly satisfactory if preoperative and postoperative level of serum CEA or CYFRA21-1 was higher than standard value, especially if the preoperative and postoperative levels of CYFRA21-1 and CEA were higher than the standard values. The measurement of preoperative and postoperative levels of CYFRA21-1 and CEA proved helpful for the prognosis of patients with NSCLC.
Background and objective Serum carcinoembryonic antigen(CEA) and the soluble fragment of cytokeratin 19(CYFRA21-1) are important tumor markers(TMs) in the preoperative examination of patients with non-small cell lung cancer(NSCLC). However, the prognostic role of these markers in NSCLC patients remains controversial. The aim of the study was to investigate the clinical significance of serum CEA variances and CYFRA21-1 levels for the prognosis of NSCLC patients following surgery. Methods This retrospective study investigated the clinical records and follow-up sessions of 175 patients with NSCLC who accepted surgery and adjuvant chemotherapy. Patients were subdivided into groups based on serum CEA and CYFRA21-1 levels. Survival analysis was conducted using Kaplan-Meier method for each group. The prognostic factor was evaluated using Cox proportional hazards model. Results The overall survival(OS) of patients with high preoperative CEA or CYFRA21-1 levels was lower than that of patients with normal preoperative CEA or CYFRA21-1 levels. The OS displayed a significant difference(P=0.001) between groups with high and normal preoperative CYFRA21-1. Compared with groups exhibiting normal preoperative and postoperative levels of CEA or CYFRA21-1, the OS was shorter for groups with high preoperative and postoperative levels of CEA or CYFRA21-1. The difference of the paired groups was significant(P<0.05). Compared with the groups with normal preoperative and postoperative levels of CEA and CYFRA21-1, the OS was lower for the groups with high preoperative and postoperative levels of CEA and CYFRA21-1, which indicated a significant difference(P<0.001). The CEACYFRA211(HHHH), CEACYFRA211(NNHH), CYFRA21-1(HH), CEA(HH), and male genderwere identified as independent prognostic factors(P<0.05). Conclusion This study suggested that the prognosis of NSCLC patients was not significantly satisfactory if preoperative and postoperative level of serum CEA or CYFRA21-1 was higher than standard value, especially if the preoperative and postoperative levels of CYFRA21-1 and CEA were higher than the standard values. The measurement of preoperative and postoperative levels of CYFRA21-1 and CEA proved helpful for the prognosis of patients with NSCLC.
引文
1 Kozu Y,Maniwa T,Tak ahashi S,et al.Prognostic signi f icance of postoperative serum carcinoembryonic antigen levels in patients with completely resected pathological-stage I non-small cell lung cancer.J Cardiothorac Surg,2013,8(1):106-112.
2 Wang CY,Huang MS,Huang MH,et al.Persistently high serum carcinoembryonic antigen levels after surgery indicate poor prognosis in patients with stage I non-small-cell lung cancer.J Surq Res,2010,163(2):45-50.
3 Matsuquma H,Nakahara R,Iqarashi S,et al.Pathologic stage I non-small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen:clinicopathologic characteristics and prognosis.J Thorac Cardiovasc Surg,2008,135(1):44-49.
4 Goldstraw P,Crowley J,Chansky K,et al.The IASLC Lung Cancer Staging Project:proposals for the revision of the TNM stage groupings in theforthcoming(seventh)edition of the TNM classification of malignant tumours.J Thorac Oncol,2007,2(8):706-714.
5 Muley T,Dienemann H,Ebert W,et al.CYFR A 21-1 and CE A are independent prognostic factors in 153 operated stage I NSCLC patients.Anticancer Res,2004,24(3B):1953-1956.
6 Pujol JL,Molinier O,Eber t W,et al.C YFR A 21-1 is a prognostic determinant in non-small-cell lung cancer:results of a meta-analysis in 2,063patients.Br J Cancer,2004,90(11):2097-2105.
7 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.Ann Thorac Surg,2004,78(1):216-221.
8 Brambi l la E,Trav i s WD,Colby T V,et al.The new World Health Organization classification of lung tumours.Eur Respir J,2001,18(6):1059-1068.
9 Lee JS,Yoon A,Kalapurakal SK,et al.Expression of P53 oncoprotein in nonsmall-cell lung cancer:A favorable prognostic factor.J Clin Oncol,1995,13(8):1893-1903.
10 Pezzella F,Turley H,Kuzu I,et al.bcl-2 protein in non-small-cell lung carcinoma.N Engl J Med,1993,329(10):690-694.
11 Hsu HS,Wen CK,Tang YA,et al.Promoter hypermethylation is the predominant mechanism in h MLH1 and h MSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer.Clin Cancer Res 2005,11(15):5410-5416.
12 Shimizu K,Yoshida J,Nagai K,et al.Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer.J Thorac Cardiovasc Surg,2005,130(1):160-165.
13 Ichinose Y,Yano T,Asoh H,et al.Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer.An analysis in each pathologic stage.J Thorac Cardiovasc Surg,1995,110(3):601-605.
14 Nagashima T,Sakao Y,Mun M,et al.A clinicopathological study of resected small-sized squamous cell carcinomas of the peripheral lung:prognostic significance of serum carcinoembr yonic antigen levels.Ann Thorac Cardiovasc Surg,2013,19(5):351-357.
15 Arrieta O,Villarreal-Garza C,Martínez-Barrera L,et al.Usefulness of serum carcinoembryonic antigen(CEA)in evaluating response to chemotherapy in patients with advanced non small-cell lung cancer:a prospective cohort study.BMC Cancer,2013,13(1):254-260.
16 Fiala O,Pesek M,Finek J,et al.Predictive role of CEA and CYFRA 21-1 in patients with advanced-stage NSCLC treated with erlotinib.Anticancer Res,2014,34(6):3205-3210.
17 Jung M,Kim SH,Lee YJ,et al.Prognostic and predictive value of CEA and CYFRA 21-1 levels in advanced non-small cell lung cancer patients treated with gefitinib or erlotinib.Exp Ther Med,2011,2(4):685-693.
18 Shoji F,Yoshino I,Yano T,et al.Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas.Cancer,2007,110(12):2793-2798.
19 Lai RS,Hsu HK,Lu JY,et al.CYFRA 21-1 enzyme-linked immunosorbent assay.Evaluation as a tumor marker in non-small cell lung cancer.Chest,1996,109(4):995-1000.
20 Pujol JL,Boher JM,Grenier J,et al.Cyfra 21-1,neuron specific enolase and prognosis of non-small cell lung cancer:prospective study in 621 patients.Lung Cancer,2001,31(2-3):221-231.
21 Reinmuth N,Brandt B,Semik M,et al.Prognostic impact of Cyfra21-1 and other serum markers in completely resected non-small cell lung cancer.Lung Cancer,2002,36(3):265-270.
22 Suzuki H,Ishikawa S,Satoh H,et al.Preoperative CYFRA 21-1 levels as a prognostic factor in c-stage I non-small cell lung cancer.Eur J Cardiothorac Surg,2007,32(4):648-652.
2 Wang CY,Huang MS,Huang MH,et al.Persistently high serum carcinoembryonic antigen levels after surgery indicate poor prognosis in patients with stage I non-small-cell lung cancer.J Surq Res,2010,163(2):45-50.
3 Matsuquma H,Nakahara R,Iqarashi S,et al.Pathologic stage I non-small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen:clinicopathologic characteristics and prognosis.J Thorac Cardiovasc Surg,2008,135(1):44-49.
4 Goldstraw P,Crowley J,Chansky K,et al.The IASLC Lung Cancer Staging Project:proposals for the revision of the TNM stage groupings in theforthcoming(seventh)edition of the TNM classification of malignant tumours.J Thorac Oncol,2007,2(8):706-714.
5 Muley T,Dienemann H,Ebert W,et al.CYFR A 21-1 and CE A are independent prognostic factors in 153 operated stage I NSCLC patients.Anticancer Res,2004,24(3B):1953-1956.
6 Pujol JL,Molinier O,Eber t W,et al.C YFR A 21-1 is a prognostic determinant in non-small-cell lung cancer:results of a meta-analysis in 2,063patients.Br J Cancer,2004,90(11):2097-2105.
7 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.Ann Thorac Surg,2004,78(1):216-221.
8 Brambi l la E,Trav i s WD,Colby T V,et al.The new World Health Organization classification of lung tumours.Eur Respir J,2001,18(6):1059-1068.
9 Lee JS,Yoon A,Kalapurakal SK,et al.Expression of P53 oncoprotein in nonsmall-cell lung cancer:A favorable prognostic factor.J Clin Oncol,1995,13(8):1893-1903.
10 Pezzella F,Turley H,Kuzu I,et al.bcl-2 protein in non-small-cell lung carcinoma.N Engl J Med,1993,329(10):690-694.
11 Hsu HS,Wen CK,Tang YA,et al.Promoter hypermethylation is the predominant mechanism in h MLH1 and h MSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer.Clin Cancer Res 2005,11(15):5410-5416.
12 Shimizu K,Yoshida J,Nagai K,et al.Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer.J Thorac Cardiovasc Surg,2005,130(1):160-165.
13 Ichinose Y,Yano T,Asoh H,et al.Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer.An analysis in each pathologic stage.J Thorac Cardiovasc Surg,1995,110(3):601-605.
14 Nagashima T,Sakao Y,Mun M,et al.A clinicopathological study of resected small-sized squamous cell carcinomas of the peripheral lung:prognostic significance of serum carcinoembr yonic antigen levels.Ann Thorac Cardiovasc Surg,2013,19(5):351-357.
15 Arrieta O,Villarreal-Garza C,Martínez-Barrera L,et al.Usefulness of serum carcinoembryonic antigen(CEA)in evaluating response to chemotherapy in patients with advanced non small-cell lung cancer:a prospective cohort study.BMC Cancer,2013,13(1):254-260.
16 Fiala O,Pesek M,Finek J,et al.Predictive role of CEA and CYFRA 21-1 in patients with advanced-stage NSCLC treated with erlotinib.Anticancer Res,2014,34(6):3205-3210.
17 Jung M,Kim SH,Lee YJ,et al.Prognostic and predictive value of CEA and CYFRA 21-1 levels in advanced non-small cell lung cancer patients treated with gefitinib or erlotinib.Exp Ther Med,2011,2(4):685-693.
18 Shoji F,Yoshino I,Yano T,et al.Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas.Cancer,2007,110(12):2793-2798.
19 Lai RS,Hsu HK,Lu JY,et al.CYFRA 21-1 enzyme-linked immunosorbent assay.Evaluation as a tumor marker in non-small cell lung cancer.Chest,1996,109(4):995-1000.
20 Pujol JL,Boher JM,Grenier J,et al.Cyfra 21-1,neuron specific enolase and prognosis of non-small cell lung cancer:prospective study in 621 patients.Lung Cancer,2001,31(2-3):221-231.
21 Reinmuth N,Brandt B,Semik M,et al.Prognostic impact of Cyfra21-1 and other serum markers in completely resected non-small cell lung cancer.Lung Cancer,2002,36(3):265-270.
22 Suzuki H,Ishikawa S,Satoh H,et al.Preoperative CYFRA 21-1 levels as a prognostic factor in c-stage I non-small cell lung cancer.Eur J Cardiothorac Surg,2007,32(4):648-652.