Cyfra21-1、ProGRP、NSE、和CEA与肺癌生物学行为关系的研究
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摘要
目的:
研究Cyfra21-1、ProGRP、NSE和CEA与肺癌生物学行为的关系,以探讨4种肿瘤标志物在肺癌辅助诊断、疗效监测、预后评估中的价值。
方法:
本研究实验对象选自某医院呼吸科2007年1月---2008年12月住院的150例肺癌患者、50例良性肺病者和80例健康体检者,①采取空腹静脉血标本,用ELISA法和电化学发光法检测血清样品中4种肿瘤标志物的含量,对检测结果进行统计学分析;②选其中完成两个周期化疗的70例患者,进行化疗前后血清4种肿瘤标志物含量的检测,分析各个指标含量的变化;③对生存大于12个月的33例和小于6个月的22例患者进行生存因素分析,分析各指标与生存的关系;④选择其中含有胸腔积液的肺癌患者50例和良性肺病30例,取空腹静脉血及胸水,检测血清和胸水中4种肿瘤标志物的含量,对检测结果进行统计学分析,同时行胸水细胞学检查。所有数据统计分析在SPSS13.0统计软件下完成。
结果:
1.肺癌患者血清Cyfra21-1、ProGRP、NSE和CEA的阳性率显著高于良性肺病组和健康体检组(P﹤0.001)。
2.肺癌患者血清Cyfra21-1、ProGRP、NSE和CEA的水平显著高于良性肺病组和健康体检组(P﹤0.001)。
3.肺癌患者中不同的组织学类型其血清Cyfra21-1、ProGRP、NSE、CEA的水平和阳性率均有差异,Cyfra21-1在非小细胞肺鳞癌中最高,明显高于肺腺癌和小细胞肺癌(P﹤0.01);NSE、ProGRP在小细胞肺癌中最高,明显高于肺腺癌和肺鳞癌(P﹤0.01);CEA在非小细胞肺腺癌中最高,与非小细胞肺鳞癌无显著差异(P>0.05),但明显高于小细胞肺癌(P﹤0.01)。
4.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA的水平和阳性率与临床分期有关。随着临床分期的增加而升高,Ⅲ期和Ⅳ期明显高于Ⅰ+Ⅱ期,血清Cyfra21-1、NSE、ProGRPⅣ期高于Ⅲ期,但无显著差异(P>0.05),血清CEAⅣ期明显高于Ⅲ期(P<0.001)。
5.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA的阳性率与年龄、性别、是否吸烟无关。
6.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA水平变化与疗效有关。疗效达CR+PR者治疗后各指标水平均比治疗前显著下降(P﹤0.05),疗效PD者Cyfra21-1、NSE、CEA水平治疗后比治疗前升高,但无显著差异(P>0. 05),ProGRP水平在治疗后虽有下降,但无显著差异(P>0. 05)。
7.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA的水平与预后有关。生存时间小于6个月的各指标水平明显高于生存大于12月者(P<0.001)。血清Cyfra21-1、CEA水平正常者大于12个月的生存率明显高于水平升高者(P<0.05)。
8.肺癌患者胸水中Cyfra21-1、ProGRP、NSE、CEA水平均高于良性肺病者,其中Cyfra21-1、CEA水平显著高于良性肺病者(P﹤0.05)。胸水CEA的ROC曲线下面积最大,其次为Cyfra21-1,两者与脱落细胞学检查的符合率均达100%。
结论:
1.血清Cyfra21-1、ProGRP、NSE、CEA与肺癌的生物学行为密切相关, Cyfra21-1在肺鳞癌中高表达, ProGRP、NSE在小细胞肺癌中高表达,CEA在腺癌中高表达,表达水平与临床分期和预后有关。
2.血清Cyfra21-1、ProGRP、NSE、CEA水平的变化与肺癌患者的疗效有关,疗效越好水平下降越明显,提示它们在肺癌治疗监测中有重要价值。
3.胸水中检测Cyfra21-1、ProGRP、NSE、CEA对鉴别良、恶性胸腔积液有重要价值,在肺癌的组织学分型中有重要意义。
Objective:
To study the relationship between on cyfra21-1 proGRP NSE CEA and biological behavior of lung cancer.To explore the clinical value of them on the diagnosis and effective detection and prodnostic evajuation of lung cancer.
Methods:
150 cases of lung cancer, 50 cases of benign disease and 50 cases of health adults were enrolled in our study.①The results of the level from serum and venous blood of four tumor markers detected by method of ELLISH were statistically analyzed.②The changes of level before and after two cycle chemotherapy of different biological markers in 70 cases from our groups were analyzed.③The prognosis of 33 cases of lung cancer who more than 12 monthsSurvival and 22 cases with less than 6 months were studied.④The levels of four tumor markers in venous blood and pleural effusion from 50 cases of lung cancer and 30 cases of benign lung disease were detected. At the same time, we conducted the exfoliation cytological examination of those malignant lung diseases. Statistical analyses were performed using SPSS 13.0 software package.
Results:
1. The positive rates of serum cyfra21-1 ProGRP NSE and CEA in cases of lung cancer were significantly higher than other two groups (P<0.001).
2. The level of four tumor markers was also significantly higher than other two groups (P<0.001).
3. The levels of four tumor markers in serum are significantly different among different pathetical types. The levels of Cyfra21-1 in squama cels carcinoma were the highest among three pathological types. NSE and ProGRP, the SCLC caught the highest levels. While the highest level of CEA belonged to the adenocarcinoma (P<0.01).
4. The serum levels and positive rates of Cyfra21-1 ProGRP NSE CEA were associated with clinical stages. With the increasing of clinical stages, the level of those four tumor markers also increasing.
5. The age sex and state of smoking showed no statistical significant with tumor marker levels.
6. The level of Cyfra21-1, ProGRP, NSE and CEA were associated with the treatment results. The level of patients achieving PR or CR after treatment was decreasing (p<0.05).
7. The serum level of Cyfra21-1 ProGRP NSE CEA was also associated with the patients prognosis (p<0.001). The tumour marker level was significant higher in patients with survival time less than 6 months than in patients with survival time more than 12 months. And that the survival rates more than 12 months was higher in patients with normal level of Cyfra21-1 ProGRP NSE CEA than in patients with higher tumour levels.
8. For levels of effusion, all of the four tumour markers show higher level in lung cancer than in benign disease. Among them, Cyfra211 and CEA were showed the most remarkable (p<0.05).
9. The area blow ROC curse put their largest one to CEA, The second was given to Cyfra21-1, The coincidence probability of these two tumour marker with the results of cytology got 100%.
Conclusion:
1. The serum level of Cyfra21-1 ProGRP NSE CEA was greatly associated with the biological behavior of lung cancer, the expression of Cyfra21-1 in squaous cells carcinoma, NSE and ProGRP in SCLC and CEA in adenocarcinoma were higher than other pathology types. The progress level is related with the clinical stage and prognosis.
2. It shows the monitoring value in progress of treatment that the relationship between the change of four tumour markers and treatment results. With the decreasing of tumour marker levels, patients may get a better survival time.
3. It shows great value for differenting from benign and malignant pleural effusion, for dignosis of pathology type by detecting the levels of Cyfra21-1 ProGRP NSE CEA.
研究Cyfra21-1、ProGRP、NSE和CEA与肺癌生物学行为的关系,以探讨4种肿瘤标志物在肺癌辅助诊断、疗效监测、预后评估中的价值。
方法:
本研究实验对象选自某医院呼吸科2007年1月---2008年12月住院的150例肺癌患者、50例良性肺病者和80例健康体检者,①采取空腹静脉血标本,用ELISA法和电化学发光法检测血清样品中4种肿瘤标志物的含量,对检测结果进行统计学分析;②选其中完成两个周期化疗的70例患者,进行化疗前后血清4种肿瘤标志物含量的检测,分析各个指标含量的变化;③对生存大于12个月的33例和小于6个月的22例患者进行生存因素分析,分析各指标与生存的关系;④选择其中含有胸腔积液的肺癌患者50例和良性肺病30例,取空腹静脉血及胸水,检测血清和胸水中4种肿瘤标志物的含量,对检测结果进行统计学分析,同时行胸水细胞学检查。所有数据统计分析在SPSS13.0统计软件下完成。
结果:
1.肺癌患者血清Cyfra21-1、ProGRP、NSE和CEA的阳性率显著高于良性肺病组和健康体检组(P﹤0.001)。
2.肺癌患者血清Cyfra21-1、ProGRP、NSE和CEA的水平显著高于良性肺病组和健康体检组(P﹤0.001)。
3.肺癌患者中不同的组织学类型其血清Cyfra21-1、ProGRP、NSE、CEA的水平和阳性率均有差异,Cyfra21-1在非小细胞肺鳞癌中最高,明显高于肺腺癌和小细胞肺癌(P﹤0.01);NSE、ProGRP在小细胞肺癌中最高,明显高于肺腺癌和肺鳞癌(P﹤0.01);CEA在非小细胞肺腺癌中最高,与非小细胞肺鳞癌无显著差异(P>0.05),但明显高于小细胞肺癌(P﹤0.01)。
4.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA的水平和阳性率与临床分期有关。随着临床分期的增加而升高,Ⅲ期和Ⅳ期明显高于Ⅰ+Ⅱ期,血清Cyfra21-1、NSE、ProGRPⅣ期高于Ⅲ期,但无显著差异(P>0.05),血清CEAⅣ期明显高于Ⅲ期(P<0.001)。
5.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA的阳性率与年龄、性别、是否吸烟无关。
6.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA水平变化与疗效有关。疗效达CR+PR者治疗后各指标水平均比治疗前显著下降(P﹤0.05),疗效PD者Cyfra21-1、NSE、CEA水平治疗后比治疗前升高,但无显著差异(P>0. 05),ProGRP水平在治疗后虽有下降,但无显著差异(P>0. 05)。
7.肺癌患者血清Cyfra21-1、ProGRP、NSE、CEA的水平与预后有关。生存时间小于6个月的各指标水平明显高于生存大于12月者(P<0.001)。血清Cyfra21-1、CEA水平正常者大于12个月的生存率明显高于水平升高者(P<0.05)。
8.肺癌患者胸水中Cyfra21-1、ProGRP、NSE、CEA水平均高于良性肺病者,其中Cyfra21-1、CEA水平显著高于良性肺病者(P﹤0.05)。胸水CEA的ROC曲线下面积最大,其次为Cyfra21-1,两者与脱落细胞学检查的符合率均达100%。
结论:
1.血清Cyfra21-1、ProGRP、NSE、CEA与肺癌的生物学行为密切相关, Cyfra21-1在肺鳞癌中高表达, ProGRP、NSE在小细胞肺癌中高表达,CEA在腺癌中高表达,表达水平与临床分期和预后有关。
2.血清Cyfra21-1、ProGRP、NSE、CEA水平的变化与肺癌患者的疗效有关,疗效越好水平下降越明显,提示它们在肺癌治疗监测中有重要价值。
3.胸水中检测Cyfra21-1、ProGRP、NSE、CEA对鉴别良、恶性胸腔积液有重要价值,在肺癌的组织学分型中有重要意义。
Objective:
To study the relationship between on cyfra21-1 proGRP NSE CEA and biological behavior of lung cancer.To explore the clinical value of them on the diagnosis and effective detection and prodnostic evajuation of lung cancer.
Methods:
150 cases of lung cancer, 50 cases of benign disease and 50 cases of health adults were enrolled in our study.①The results of the level from serum and venous blood of four tumor markers detected by method of ELLISH were statistically analyzed.②The changes of level before and after two cycle chemotherapy of different biological markers in 70 cases from our groups were analyzed.③The prognosis of 33 cases of lung cancer who more than 12 monthsSurvival and 22 cases with less than 6 months were studied.④The levels of four tumor markers in venous blood and pleural effusion from 50 cases of lung cancer and 30 cases of benign lung disease were detected. At the same time, we conducted the exfoliation cytological examination of those malignant lung diseases. Statistical analyses were performed using SPSS 13.0 software package.
Results:
1. The positive rates of serum cyfra21-1 ProGRP NSE and CEA in cases of lung cancer were significantly higher than other two groups (P<0.001).
2. The level of four tumor markers was also significantly higher than other two groups (P<0.001).
3. The levels of four tumor markers in serum are significantly different among different pathetical types. The levels of Cyfra21-1 in squama cels carcinoma were the highest among three pathological types. NSE and ProGRP, the SCLC caught the highest levels. While the highest level of CEA belonged to the adenocarcinoma (P<0.01).
4. The serum levels and positive rates of Cyfra21-1 ProGRP NSE CEA were associated with clinical stages. With the increasing of clinical stages, the level of those four tumor markers also increasing.
5. The age sex and state of smoking showed no statistical significant with tumor marker levels.
6. The level of Cyfra21-1, ProGRP, NSE and CEA were associated with the treatment results. The level of patients achieving PR or CR after treatment was decreasing (p<0.05).
7. The serum level of Cyfra21-1 ProGRP NSE CEA was also associated with the patients prognosis (p<0.001). The tumour marker level was significant higher in patients with survival time less than 6 months than in patients with survival time more than 12 months. And that the survival rates more than 12 months was higher in patients with normal level of Cyfra21-1 ProGRP NSE CEA than in patients with higher tumour levels.
8. For levels of effusion, all of the four tumour markers show higher level in lung cancer than in benign disease. Among them, Cyfra211 and CEA were showed the most remarkable (p<0.05).
9. The area blow ROC curse put their largest one to CEA, The second was given to Cyfra21-1, The coincidence probability of these two tumour marker with the results of cytology got 100%.
Conclusion:
1. The serum level of Cyfra21-1 ProGRP NSE CEA was greatly associated with the biological behavior of lung cancer, the expression of Cyfra21-1 in squaous cells carcinoma, NSE and ProGRP in SCLC and CEA in adenocarcinoma were higher than other pathology types. The progress level is related with the clinical stage and prognosis.
2. It shows the monitoring value in progress of treatment that the relationship between the change of four tumour markers and treatment results. With the decreasing of tumour marker levels, patients may get a better survival time.
3. It shows great value for differenting from benign and malignant pleural effusion, for dignosis of pathology type by detecting the levels of Cyfra21-1 ProGRP NSE CEA.
引文
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[1]HsuWH,HuangCS,HsuHS,etal.Preoperative serum carcinoem bryonic antigen level is a prognostic factor in women with early non small cell lung cancer〔J〕.Ann Thorac Surg,2007,83(2):419.
[2]许杰,杜俊峰,彭心宇,等.联合检测肿瘤标志物在肺癌诊断中的临床价值[J].现代肿瘤医学,2008,16(4):645.
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[4]TamuraM,OhtaY,NakamuraH,et al.Diagnostic v alue of plasma vascular endothelial growth factor asatumor marker in patients with non small cell lung cancer Int [J].Biol Mark ers,2002,17(4):275 297
[5]KidoY.Vascular endothelial growth factor(VEGF) serum concentration changes during chemotherapy in patients with lung cancer KurumeMedJ,2001,48(1):43 47
[6]李雪冰,李宝兰,赖百塘,等.肺癌患者血清MMP29,Endostatin,VEGF水平及临床意义[J].结核病与肺部肿瘤,2005,3(9):170-173.
[7]Poon RT ,Fan ST ,Wong J . Clinical implications lf circulating angiogenic factors in cancer patients[J ] . Clin Oncol ,2001 ,19(4) :1207.
[8]杨谨,李蓉,李昂,等胃泌素释放肽前体片段31 98检测对小细胞肺癌的临床意义[J].中华肿瘤杂志,2000,22(3):216-218
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[10] Shitrit D,Zingerman B,Shitrit AB,et al. Diagnostic value of CYFRA21-1,CEA,CA19 9,CA153,andCA125 assay sinpleural effusions:analysis of 116 cases and review of the literature Oncologist,2005,10(7):501 507
[11]Alatas F,AlatasO,MetintasM. Diagnostic value of CEA, CA153,CA199,CYFRA21 - 1,NSE and TSA, assay inp leural effusions [ J ].Lung Cancer, 2001, 31 (1) : 9.
[12]高云朝,王美琴,陆云,等.血清肿瘤标志物检测对肺癌患者的检测价值[J].中华结核和呼吸杂志.2005,28(4):268 269
[13]谢艳茹,周月芬,王永辉,等.肺癌患者血清CA125水平变化及临床意义〔J〕.浙江中西医结合杂志,2006,16(3):143.
[14]Ylisirnio S,Hoyhtya M,Makitaro R,et al.Elevated serum level softyp collagen degradation marker ICTP and tissue inhibitor of metal oproteinase (TIMP) 1 are associated with poor prognosis in lung cancer ClinCancerRes,2001,7(76):1633 1637
[15]Ylisirnio S,Hoyhtya M,Turpeenniemi HS. Erummatrix metal oproteinases 2,9 and tissue inhibitors of metal protein ases1,2 in lung cancer TIMP 1asaprognostic marker An tic ancer Res,2000,20(2B):1311- 1316
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