-
近年来,随着核医学、分子生物学和影像学技术的发展,对肺癌的诊断具有许多新的认识和进展。肺癌是当今世界上发病率和病死率最高的恶性肿瘤,全世界死于肿瘤的患者中大约三分之一死于肺癌[1],且呈上升趋势。肺癌起病一般比较隐匿,70%~80%的肺癌患者确诊时已属晚期,由于肺癌的诊治延误、转移和多耐药性等原因,治愈率很低,目前总的5年生存率仅13%~15%,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)5年生存率<10%,小细胞肺癌(small cell lung cancer,SCLC)<3%。临床上广泛应用的肿瘤标志物为癌胚抗原、糖链抗原(carbohydrate antigen,CA)199、神经元特异性烯醇化酶(neuron-specific enolase,NSE)、鳞状细胞癌相关抗原(squamous cell carcinoma antigen,SCC)和肿瘤多肽抗原等,其灵敏度、特异度和准确率都不甚理想,因此当务之急是寻找新的诊断指标,以期达到早期发现、早期诊断、早期治疗之目的,以便Ⅰ期肺癌术后5年生存率达到60%~90%[2]。
-
从表 1可见,184例肺癌患者的血浆CYFRA21-1水平与51例肺部良性疾病患者(t=5.637,P<0.001)、60名正常对照者(t=8.612,P<0.001)相比,均明显升高,其中,81例鳞癌患者升高最为明显: 24例Ⅰ~Ⅱ期和57例Ⅲ~Ⅳ期肺鳞癌患者的血浆CYFRA21-1水平分别为(26.32±15.16) μg/L和(81.02±21.16) μg/L,与51例肺部良性疾病患者相比均明显升高(tⅠ~Ⅱ=4.436,P<0.01,tⅢ~Ⅳ=10.147,P<0.001)。184例肺癌患者血浆CA125、CA199和CA153水平与51例肺部良性疾病患者(tCA125=3.106,P<0.01;tCA199=4.456,P<0.001;tCA153=3.763,P<0.01)、60名正常对照者相比均显著升高(tCA125=4.067,tCA199=4.872,tCA153=8.673,P均<0.001),其中,与60名正常对照者相比,68例肺腺癌患者升高最为明显: 21例肺腺癌患者的血浆CA125、CA199和CA153水平分别为(27.36±18.62) U/ml(tCA125=2.865,P<0.01)、(36.19±25.67) U/ml(tCA199=2.931,P<0.01)和(41.45±23.2) U/ml(tCA153=3.156,P<0.01),而47例Ⅲ~Ⅳ期肺腺癌患者分别为(81.56±38.15) U/ml(tCA125=8.436,P<0.001)、(132.10±59.66) U/ml(tCA199=11.764,P<0.001)和(133.75±56.60) U/ml(tCA153=12.043,P<0.001)。与60名正常对照者相比,51例肺部良性疾病患者的血浆CYFRA21-1水平显著升高(tCYFRA21-1=6.327,P<0.001);CA125和CA153水平升高(tCA125=2.264,tCA153=2.343,P均<0.05);CA199水平差异无统计学意义(tCA199=1.761,P>0.05)。
组别 例数 CYFRA21-1(μg/L) CA125(U/ml) CA199(U/ml) CA153(U/ml) 肺癌患者 184 50.84±17.02***(8.612) 49.18±25.54***(4.067) 67.48±33.60***(4.872) 82.48±40.05***(8.673) 鳞癌患者 81 65.71±19.64***(9.324) 39.62±19.88***(3.675) 51.38±25.27***(3.942) 70.18±37.49***(7.813) 腺癌患者 68 43.68±16.34***(7.821) 64.37±30.15***(5.187) 101.36±51.24***(7.816) 110.49±49.16***(9.068) SCLC患者 35 30.36±12.32***(7.125) 41.85±20.37***(7.843) 38.95±18.66**(3.139) 56.57±28.52***(6.183) 肺部良性疾病患者 51 7.69±3.54***(6.327) 22.81±10.49*(2.264) 20.63±10.15Δ(1.761) 32.17±21.24*(2.343) 正常对照者 60 1.80±0.75 18.34±7.12 19.21±9.02 20.11±9.25 注:表中,CYFRA21-1:细胞角蛋白19片段; CA:糖链抗原; SCLC:小细胞肺癌; 与正常对照者比较,△P>0.05,*P<0.05,**P<0.01,***P<0.001;括号内的数据均为与正常对照者比较的t值。 表 1 184例肺癌患者、51例肺部良性疾病患者和60名正常对照者的血浆CYFRA21-1、CA125、CA199、CA153水平
Table 1. The CYFRA21-1, CA125, CA199 and CA153 levels in 184 cases lung cancer, 51 cases benign lung disease and 60 controls
(x±s) -
从表 2可知,在四项肿瘤标志物中,CYFRA21-1的灵敏度最高,特异度最低,CA199灵敏度和准确率均最低,而特异度最高。
肿瘤标志物 灵敏度(%) 特异度(%) 准确率(%) CYFRA21-1 59.78(110/184) 19.82(22/111) 70.17(207/295) CA125 48.37(89/184) 25.33(28/111) 64.07(189/295) CA199 30.43(56/184) 28.83(32/111) 50.84(150/295) CA153 34.78(64/184) 20.72(23/111) 54.91(162/295) 注:表中,CYFRA21-1:细胞角蛋白19片段;CA:糖链抗原。 表 2 单项肿瘤标志物在肺癌诊断中的效果比较
Table 2. Value of single tumor marker on lung cancer diagnosis
-
从表 3可知,两项肿瘤标志物检测与单项检测比较,灵敏度明显增高,两项检测以CYFRA21-1+CA125的灵敏度和准确率为最高,CA125+CA199特异度最高。
肿瘤标志物 灵敏度(%) 特异度(%) 准确率(%) CYFRA21-1+CA125 79.35(146/184) 28.83(32/111) 82.03(242/295) CYFRA21-1+CA199 64.13(118/184) 34.23(38/111) 72.88(215/295) CYFRA21-1+CA153 71.74(132/184) 23.42(26/111) 69.83(206/295) CA125+CA199 61.41(113/184) 36.04(40/111) 72.20(213/295) CA125+CA153 60.32(111/184) 27.03(30/111) 68.81(203/295) CA199+CA153 54.89(101/184) 29.73(33/111) 66.78(197/295) 注:表中,CYFRA21-1:细胞角蛋白19片段;CA:糖链抗原。 表 3 两项肿瘤标志物在肺癌诊断中的效果比较
Table 3. Value of combination of two tumor markers on lung cancer diagnosis
-
从表 4可知,三项检测以CA125 +CA199+CA153特异度为最高,CYFRA21-1+CA125+CA199的灵敏度和准确率最高。四项CYFRA21-1+CA125+CA199+CA153联合检测效果最佳,其灵敏度高达93.48%,特异度为33.33%,准确率为86.44%。
肿瘤标志物 灵敏度(%) 特异度(%) 准确率(%) CYFRA21-1+CA125+CA199 87.50(161/184) 31.53(35/111) 84.07(248/295) CYFRA21-1+CA199+CA153 84.78(156/184) 36.04(40/111) 81.02(239/295) CA125+CA199+CA153 72.83(134/184) 37.84(42/111) 71.86(212/295) CYFRA21-1+CA125+CA199+CA153 93.48(172/184) 33.33(37/111) 86.44(255/295) 注:表中,CYFRA21-1:细胞角蛋白19片段; CA:糖链抗原。表 2、表 3、表 4计算公式参考文献[10]。 表 4 三项和三项以上肿瘤标志物在肺癌诊断中的效果比较
Table 4. Value of combination of more than three tumor markers on lung cancer diagnosis
-
从图 1和表 5可知,肺癌患者的CYFRA21-1诊断曲线下面积明显大于CA125、CA199和CA153,并优于其他肿瘤标志物(AUC: 0.889,P<0.001),95%可信区间为0.884~0.895。
图 1 各肿瘤标志物诊断肺癌的受试者工作特征曲线
Figure 1. Receiver operating characteristic curve of every tumor marker of lung cancer diagnosis
肿瘤标志物 AUC(95%可信区间) P值 临界值(cut-off值) 灵敏度(%) 特异度(%) CYFRA21-1 0.889(0.884~0.895) <0.001(t=5.364) 65.4 μg/L 84.8 93.9 CA125 0.732(0.721~0.804) <0.01(t=3.216) 71.2 U/ml 64.7 74.8 CA199 0.721(0.704~0.812) <0.01(t=3.187) 80.3 U/ml 59.8 82.0 CA153 0.718(0.705~0.804) <0.05(t=2.153) 107.4 U/ml 54.9 79.3 注:表中,CYFRA21-1:细胞角蛋白19片段;CA:糖链抗原;AUC:曲线下面积。 表 5 四项肿瘤标志物预测肺癌的性能评价
Table 5. Value of four tumor markers prediction efficiency on lung cancer diagnosis
血浆CYFRA21-1和CA125、CA199、CA153联合检测对肺癌的辅助诊断价值
The value of combined detection of plasma CYFRA21-1 and CA125, CA199, CA153 in the accessory diagnosis of lung cancer
-
摘要:
目的 探讨血浆细胞角蛋白19片段(CYFRA21-1)和糖链抗原肿瘤标志物水平测定对肺癌诊断的临床意义。 方法 采用放射免疫分析法和化学发光免疫法检测了184例肺癌患者(包括81例肺鳞癌、68例肺腺癌和35例小细胞肺癌患者)的血浆CYFRA21-1和糖链抗原125、199和153(CA125、CA199和CA153)水平,并与51例肺部良性疾病患者和60名正常对照者进行了比较性分析; 进行了肿癌标志物诊断肺癌的不同联合测定情况下的灵敏度、特异度和准确率的比较。 结果 与51例肺部良性疾病患者相比,184例肺癌患者的血浆CYFRA21-1、CA125、CA199和CA153水平显著升高(tCYFRA21-1=5.637,P<0.001;tCA125=3.106,P<0.01;tCA199=4.456,P<0.001;tCA153=3.763,P<0.01)。与60名正常对照者相比,184例肺癌患者的血浆CYFRA21-1、CA125、CA199和CA153水平显著升高(tCYFRA21-1=8.612,tCA125=4.067,tCA199=4.872,tCA153=8.673,P均<0.001)。与60名正常对照者相比,51例肺部良性疾病患者的血浆CYFRA21-1水平显著升高(tCYFRA21-1=6.327,P<0.001);CA125和CA153水平升高(tCA125=2.264,tCA153=2.343,P均<0.05);CA199水平差异无统计学意义(tCA199=1.761,P>0.05)。在184例肺癌中,81例肺鳞癌患者的血浆CYFRA21-1水平升高最为显著,68例肺腺癌患者的血浆CA125、CA199和CA153水平升高最为明显。单项肿瘤标志物检测CYFRA21-1的灵敏度(59.78%)和准确率(70.17%)最好,CA199的特异度(28.83%)最高。而四项联合检测肺癌的灵敏度(93.48%)和准确率(86.44%)为最高,明显高于单项和两项的检测。 结论 血浆CYFRA21-1、CA125、CA199和CA153水平测定是诊断肺癌的有价值肿瘤标志物,它们的联合测定可以提高诊断灵敏度和准确率。 Abstract:Objective To explore the clinical significance of combined detection of plasma (cytokerantin-19-fragment, CYFRA21-1) and carbohydrate antigen tumor markers levels for lung cancer diagnosis. Methods The plasma CYFRA21-1 and carbohydrate antigen(CA125, CA199 and CA153) levels were measured with radio immunoassay and chemiluminescent immunoassay in 184 patients with lung cancer(including 81 cases of lung squanous carcinoma, 68 cases of adeno-carcinoma, 35 cases of small cell lung cancer), and then compared with 51 patients with benign lung disease and 60 healthy controls.The sensitivities, specificities and accuracies of different combination of those markers for the diagnosis of lung cancer were compared. Results The plasma CYFRA21-1 and carbohydrate antigen(CA125, CA199 and CA153) levels in 184 patients with lung cancer were significantly higher than those in 51 patients with benign lung disease(tCYFRA21-1=5.637, P < 0.001; tCA125=3.106, P < 0.01; tCA199=4.456, P < 0.001; tCA153=3.763, P < 0.01) and 60 healthy controls(tCYFRA21-1=8.612, tCA125=4.067, tCA199=4.872, tCA153=8.673, all P < 0.001).Compared with the 60 healthy controls, plasma levels of CYFRA21-1 in 51 cases with benign lung disease were significantly higher(tCYFRA21-1=6.327, P < 0.001); CA125 and CA153 levels were increased(tCA125=2.264, tCA153=2.343, P < 0.05); and there are no significant difference in CA199 levels(tCA199=1.761, P>0.05).In 184 lung cancer patients, the plasma CYFRA21-1 levels in 81 patients with lung squanous-carcinoma was the highest, but the plasma CA125, CA199, and CA153 levels in 68 patients with lung sdeno-careinoma were the highest.The CYFRA21-1 had the highest sensitivity(59.78%) and accuracy(70.17%) and CA199 had the highest specificity(28.83%) for detecting lung cancer.The combined detection of the four items has the highest sensitivity and accuracy(93.48% and 86.44%) in the diagnosis of lung cancer, obviously higher than single or two items combined detection. Conclusions The plasma CYFRA21-1, CA125, CA199 and CA153 were valuable tumor markers for the diagnosis of lung cancer.The combination of the tumor markers could improve the diagnostic sensitivity and accuracy. -
Key words:
- Lung neoplasms /
- Keratin /
- CA-125 antigen /
- CA-199 antigen /
- CA-153 antigen /
- Radioimmunoassay /
- Chemiluminescent measurements
-
表 1 184例肺癌患者、51例肺部良性疾病患者和60名正常对照者的血浆CYFRA21-1、CA125、CA199、CA153水平
Table 1. The CYFRA21-1, CA125, CA199 and CA153 levels in 184 cases lung cancer, 51 cases benign lung disease and 60 controls
(x±s) 组别 例数 CYFRA21-1(μg/L) CA125(U/ml) CA199(U/ml) CA153(U/ml) 肺癌患者 184 50.84±17.02***(8.612) 49.18±25.54***(4.067) 67.48±33.60***(4.872) 82.48±40.05***(8.673) 鳞癌患者 81 65.71±19.64***(9.324) 39.62±19.88***(3.675) 51.38±25.27***(3.942) 70.18±37.49***(7.813) 腺癌患者 68 43.68±16.34***(7.821) 64.37±30.15***(5.187) 101.36±51.24***(7.816) 110.49±49.16***(9.068) SCLC患者 35 30.36±12.32***(7.125) 41.85±20.37***(7.843) 38.95±18.66**(3.139) 56.57±28.52***(6.183) 肺部良性疾病患者 51 7.69±3.54***(6.327) 22.81±10.49*(2.264) 20.63±10.15Δ(1.761) 32.17±21.24*(2.343) 正常对照者 60 1.80±0.75 18.34±7.12 19.21±9.02 20.11±9.25 注:表中,CYFRA21-1:细胞角蛋白19片段; CA:糖链抗原; SCLC:小细胞肺癌; 与正常对照者比较,△P>0.05,*P<0.05,**P<0.01,***P<0.001;括号内的数据均为与正常对照者比较的t值。 表 2 单项肿瘤标志物在肺癌诊断中的效果比较
Table 2. Value of single tumor marker on lung cancer diagnosis
肿瘤标志物 灵敏度(%) 特异度(%) 准确率(%) CYFRA21-1 59.78(110/184) 19.82(22/111) 70.17(207/295) CA125 48.37(89/184) 25.33(28/111) 64.07(189/295) CA199 30.43(56/184) 28.83(32/111) 50.84(150/295) CA153 34.78(64/184) 20.72(23/111) 54.91(162/295) 注:表中,CYFRA21-1:细胞角蛋白19片段;CA:糖链抗原。 表 3 两项肿瘤标志物在肺癌诊断中的效果比较
Table 3. Value of combination of two tumor markers on lung cancer diagnosis
肿瘤标志物 灵敏度(%) 特异度(%) 准确率(%) CYFRA21-1+CA125 79.35(146/184) 28.83(32/111) 82.03(242/295) CYFRA21-1+CA199 64.13(118/184) 34.23(38/111) 72.88(215/295) CYFRA21-1+CA153 71.74(132/184) 23.42(26/111) 69.83(206/295) CA125+CA199 61.41(113/184) 36.04(40/111) 72.20(213/295) CA125+CA153 60.32(111/184) 27.03(30/111) 68.81(203/295) CA199+CA153 54.89(101/184) 29.73(33/111) 66.78(197/295) 注:表中,CYFRA21-1:细胞角蛋白19片段;CA:糖链抗原。 表 4 三项和三项以上肿瘤标志物在肺癌诊断中的效果比较
Table 4. Value of combination of more than three tumor markers on lung cancer diagnosis
肿瘤标志物 灵敏度(%) 特异度(%) 准确率(%) CYFRA21-1+CA125+CA199 87.50(161/184) 31.53(35/111) 84.07(248/295) CYFRA21-1+CA199+CA153 84.78(156/184) 36.04(40/111) 81.02(239/295) CA125+CA199+CA153 72.83(134/184) 37.84(42/111) 71.86(212/295) CYFRA21-1+CA125+CA199+CA153 93.48(172/184) 33.33(37/111) 86.44(255/295) 注:表中,CYFRA21-1:细胞角蛋白19片段; CA:糖链抗原。表 2、表 3、表 4计算公式参考文献[10]。 表 5 四项肿瘤标志物预测肺癌的性能评价
Table 5. Value of four tumor markers prediction efficiency on lung cancer diagnosis
肿瘤标志物 AUC(95%可信区间) P值 临界值(cut-off值) 灵敏度(%) 特异度(%) CYFRA21-1 0.889(0.884~0.895) <0.001(t=5.364) 65.4 μg/L 84.8 93.9 CA125 0.732(0.721~0.804) <0.01(t=3.216) 71.2 U/ml 64.7 74.8 CA199 0.721(0.704~0.812) <0.01(t=3.187) 80.3 U/ml 59.8 82.0 CA153 0.718(0.705~0.804) <0.05(t=2.153) 107.4 U/ml 54.9 79.3 注:表中,CYFRA21-1:细胞角蛋白19片段;CA:糖链抗原;AUC:曲线下面积。 -
[1] 白孝雪, 张研蓓.肺癌肿瘤标志物检测的研究现状[J].临床肺科杂志, 2011, 16(2): 259-260.
[2] 刘红, 李海燕, 王静, 等.肿瘤标志物联合胸部影像学在肺癌早期诊断中的价值[J].实用医学杂志, 2012, 28(12): 2078-2080.
[3] Kasprzak A, Zabel M, Biczysko W.Selected markers(Chromogranin A, neuron-specific enolase, Synaptophysin, proteingene product 9.5)in diagnosis of neuroendocrine pulmonary tumours[J].Pol J pathol, 2007, 58(1): 23-33. [4] Ekman S, Eriksson P, Bergstron S, et al.Clinical value of using serological cytokeratins of therspcific markers in thoracic malignancie[J].Anticancer Res, 2007, 27(58): 3545-3553. [5] Monteiro E, Varzim G, Crespo M, et al.Varzim GME, CYFRA21-1, TPS and SCC in Squamous cell carcinoma larynx[J].An Otorrinlaringol Ibero Am, 2003, 30(5): 4674-4679. [6] Haizakis KD, Froudarakis ME, Bouros D, et al.Prognosic value of serum tumor markers in patients with lung cancer[J].Respiration, 2002, 69(1): 26-37. [7] Shitrit D, Zingerman B, Shitrit AB, et al.Diagnostic Value of CYFRA21-1, CEA, CA19-9, CA15-3, CA125 assay in pleural effusion: analysis of 116 cases and review of the litersture[J].Oncologist, 2005, 10(2): 501-507. [8] 郝青林, 孙士波, 谭波, 等.糖类抗原联合检测对肺癌合并胸腔积液的诊断价值[J].国际呼吸杂志, 2008, 28(18): 1094-1096.
[9] Schiller JH, Harring TD, Belani CP, et al.Comparison of four chemotherapy regimens for advanced non-small cell lung cancer[J].N Engl J Med, 2002, 346(2): 92-98. [10] Ustiln H, Borazan A, Bilgicli N, et al.Diagnostic value of tumoural markers in pleural effusions[J].Int J Clin Pract, 2004, 58: 22-25. [11] Takahide K, Hiroaki S, Hiroichi I, et al.Serum of CA19-9 in patients with nonmalignant respiratory disease[J].J Clin Lab Anal, 2007, 21(2): 103-106. [12] 陈铎, 李为民, 王冬梅, 等.联合检测血清肿瘤标志物在肺癌诊断中的价值[J].四川大学学报:医学版, 2008, 39(5): 832-835.
[13] Li CS, Cheng BC, Ge W, et al.Clinical value of CYFRA21-1, NSE, CA153, CA199, CA125 assay in the elderly patients with pleural effusions.Int J Clin Pract[J].2007, 61(3): 444-448.