血清bFGF、MMP-2与鼻咽癌浸润转移的相关性研究
摘要
目的:检测bFGF(Basic fibroblast growth factor碱性成纤维细胞生长因子)、MMP-2(Matrix metalloproteinase-2基质金属蛋白酶-2)在鼻咽癌(Nasopharyngeal carcinoma,NPC)放疗前后血清中的表达水平,探讨上述指标与鼻咽癌的发生发展及浸润转移的相关性。
方法:采用酶联免疫吸附试验(Enzyme-linked immunosorbent,ELISA)方法分别检测63例鼻咽癌患者放疗前后及20例健康体检者血清bFGF、MMP-2水平,比较2个指标的表达水平与鼻咽癌放疗前后及放疗前分期的关系。
结果:
1、鼻咽癌患者放疗前血清bFGF、MMP-2表达水平分别为别为5.1535±2.2745(ng/ml)、164.0763±64.6049(ng/ml),明显高于健康体检者2.1035±0.3048(ng/ml)、85.7873±6.7371(ng/ml)(p<0.01)。也明显高于同组患者放疗后血清bFGF、MMP-2表达水平2.5141±1.2719(ng/ml)、97.4158±48.6825(ng/ml)(p<0.01)。鼻咽癌患者放疗后血清bFGF、MMP-2表达水平虽比健康体检者高,但差异无统计学意义(p>0.05)。
2、bFGF、MMP-2的表达水平与鼻咽癌患者性别无关(p>0.05)。
3、鼻咽癌患者放疗前血清bFGF、MMP-2表达水平与临床分期、TNM分期有关,并随着临床分期、TNM分期的增加而增加。
4、鼻咽癌患者放疗前血清bFGF、MMP-2表达水平呈正相关(r=0.8748,p<0.01)。
结论:血清中的bFGF、MMP-2的表达水平在一定程度上反映了鼻咽癌发生、发展、浸润转移情况,联合检测bFGF、MMP-2具有协同评估作用,对鼻咽癌的诊断、转移和预后的预测可能具有重要参考价值。
Objective:Detect the Basic fibroblast growth factor(bFGF)、Matrix metalloproteinase-2(MMP-2)express levels detection in Patients's serum of nasopharyngeal carcinoma before and after radiotherapy。Discuss the correlative research for bFGF、MMP-2 in infiltraive transfer of in Patients's serum of nasopharyngeal carcinoma。
Methods:bFGF、MMP-2 express levels in serum were determinded in 63 same NPC patient before and after radiotherapy by Enzyme-linked immunosorbent(ELISA),contemporary the 20 healthy check-up people were determinded。The relationshipn between the express levels of bFGF、MMP-2 in NPC patient before and after radiotherapy and different clinic stages of NPC before radiotherapy were compared。
Results:
1、The express levels of bFGF、MMP-2 before radiotherapy in NPC patients's serum were 5.1535±2.2745(ng/ml)、164.0763±64.6049(ng/ml), higher than healthy check-up people's serum 2.1035±0.3048(ng/ml)、85.7873±6.7371(ng/ml)(p＜0.01),also higher than same nasopharyngeal carcinoma afer radiotherapy 2.5141±1.2719(ng/ml)、97.4158±48.6825 (ng/ml)(p＜0.01)。Although the express levels ofbFGF、MMP-2 in NPC patients's serum afer radiotherapy higher than the healthy for check-up people,there were out of statistice meaning(p＞0.05)。
2、The express levels of bFGF、MMP-2 in NPC patients's serum were irrelative to sex。
3、The express levels of bFGF、MMP-2 in NPC patients's serum increase with the stage of tunmor clinic and TNM stages rasing。
4、The express levels of bFGF、MMP-2 have positively sensitivity relationship existed in NPC patients's serum before radiotherapy (r=0.8748,p＜0.01)。
Conclusion:The resules indicated that there were definite value in detection of bFGF、MMP-2 express levels for the happen、the development、the infiltraive and the transfer of the nasopharyngeal carcinoma patients。There are some estimate value to check the express levels of bFGF、MMP-2 with combine。There are maybe some important value in diagnose、transfer and recrudesce after therapy for NPC。
方法:采用酶联免疫吸附试验(Enzyme-linked immunosorbent,ELISA)方法分别检测63例鼻咽癌患者放疗前后及20例健康体检者血清bFGF、MMP-2水平,比较2个指标的表达水平与鼻咽癌放疗前后及放疗前分期的关系。
结果:
1、鼻咽癌患者放疗前血清bFGF、MMP-2表达水平分别为别为5.1535±2.2745(ng/ml)、164.0763±64.6049(ng/ml),明显高于健康体检者2.1035±0.3048(ng/ml)、85.7873±6.7371(ng/ml)(p<0.01)。也明显高于同组患者放疗后血清bFGF、MMP-2表达水平2.5141±1.2719(ng/ml)、97.4158±48.6825(ng/ml)(p<0.01)。鼻咽癌患者放疗后血清bFGF、MMP-2表达水平虽比健康体检者高,但差异无统计学意义(p>0.05)。
2、bFGF、MMP-2的表达水平与鼻咽癌患者性别无关(p>0.05)。
3、鼻咽癌患者放疗前血清bFGF、MMP-2表达水平与临床分期、TNM分期有关,并随着临床分期、TNM分期的增加而增加。
4、鼻咽癌患者放疗前血清bFGF、MMP-2表达水平呈正相关(r=0.8748,p<0.01)。
结论:血清中的bFGF、MMP-2的表达水平在一定程度上反映了鼻咽癌发生、发展、浸润转移情况,联合检测bFGF、MMP-2具有协同评估作用,对鼻咽癌的诊断、转移和预后的预测可能具有重要参考价值。
Objective:Detect the Basic fibroblast growth factor(bFGF)、Matrix metalloproteinase-2(MMP-2)express levels detection in Patients's serum of nasopharyngeal carcinoma before and after radiotherapy。Discuss the correlative research for bFGF、MMP-2 in infiltraive transfer of in Patients's serum of nasopharyngeal carcinoma。
Methods:bFGF、MMP-2 express levels in serum were determinded in 63 same NPC patient before and after radiotherapy by Enzyme-linked immunosorbent(ELISA),contemporary the 20 healthy check-up people were determinded。The relationshipn between the express levels of bFGF、MMP-2 in NPC patient before and after radiotherapy and different clinic stages of NPC before radiotherapy were compared。
Results:
1、The express levels of bFGF、MMP-2 before radiotherapy in NPC patients's serum were 5.1535±2.2745(ng/ml)、164.0763±64.6049(ng/ml), higher than healthy check-up people's serum 2.1035±0.3048(ng/ml)、85.7873±6.7371(ng/ml)(p＜0.01),also higher than same nasopharyngeal carcinoma afer radiotherapy 2.5141±1.2719(ng/ml)、97.4158±48.6825 (ng/ml)(p＜0.01)。Although the express levels ofbFGF、MMP-2 in NPC patients's serum afer radiotherapy higher than the healthy for check-up people,there were out of statistice meaning(p＞0.05)。
2、The express levels of bFGF、MMP-2 in NPC patients's serum were irrelative to sex。
3、The express levels of bFGF、MMP-2 in NPC patients's serum increase with the stage of tunmor clinic and TNM stages rasing。
4、The express levels of bFGF、MMP-2 have positively sensitivity relationship existed in NPC patients's serum before radiotherapy (r=0.8748,p＜0.01)。
Conclusion:The resules indicated that there were definite value in detection of bFGF、MMP-2 express levels for the happen、the development、the infiltraive and the transfer of the nasopharyngeal carcinoma patients。There are some estimate value to check the express levels of bFGF、MMP-2 with combine。There are maybe some important value in diagnose、transfer and recrudesce after therapy for NPC。
引文
1 闵华庆.未经放疗、化疗及手术治疗的Ⅲ、Ⅳ期鼻咽癌81例生存期统计.新医学,1973,4:197-198.
2 陈春燕,卢泰祥.局部晚期鼻咽癌治疗新进展.中国癌症杂志,2006,16(6):437-441.
3 曾益新,主编.肿瘤学[M].北京:人民卫生出版社,2001:177-179.
4 Harlozinska A.Progress in molecular mechanisms of tumor metastasis and angiogenesis[J].Anticancer Res,2005,25(5):3327-3333.
5 赵军,刘叙仪,张青云,等.晚期非小细胞肺癌患者外周血VEGF和bFGF及MMP-9水平与预后的关系[J].中华肿瘤杂志,2005,27(11):676-679.
6 郭新,李玉林,张丽红,等.胃癌组织碱性成纤维细胞生成因子表达及对血管新生和肿瘤进展的影响[J].中华消化杂志,2002:22(4):209-212.
7 陈洪雷,刁路明,刘铭球,等.MMP2、TIMP2、bFGF在大鼠肺鳞癌癌变过程中的动态表达.肿瘤,2002,22(5):375-378.
8 Wilkie AO,Patey SJ,Kan SH FGFs,their receptors,and human limb malformations:clinical and molecular correlations.Am J Med Genet,2002,12(3):266-278.
9 Abuhaibeid S,Czubayko F,Aiqner A.The fibroblast growth factor-binding protein FGF-BP[J].Int J Biochem Cell Biol, 2006,38(9):1463-1468.
10 Pallares J,Rojo F,Iriarte J,et al.Study of micmvessel density and the expression of the angiogenic factors VEGF,bFGF and the receptors Flt-1 and FLK-1 in benign,premalignant an d malignant prostate tissues[J].2006,21(8):857-865.
11 Frank Riedel,Karl Gotte,Wolfgang Bergler,et al.Expression fbasic fibroblast growth factor protein and its down-regulation by intelfemns in head and neck cancer[J].Head & Neck,2000,22(2):183-189.
12 Hase T,Kawashiri S,Tanaka A,et al.Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of Oral squamous cell carcinoma[J].Oral Pathol Med,2006,35(3):136-139.
13 Veselv D,Am J,Matucha P,et al.Serum levels of angiogenic growth factors in patients with thyroid gland tumors and parathyroid adenoma[J].Neuro Endocrinol Lett,2003,24(6):417-419.
14 Homer JJ.Greenman J,Staford ND.Circulating angiogenic cyto'kines as tumour markers an d prognostic factors in head and neck squamous cell carcinoma[J].Clin Otolaryngol Allied Sci,2002,27(1):32-37.
15 Li C,Shintani S,Terakado N,et al.Micmvessel density and expression of vascular endothelial growth factor,basic fibmblast growth factor,and platelet-derived endothelial growth factor in oral squamous cell carcinomas[J].Int J Oral Maxillofac Surg,2005,34(5):559-565.
16 Liang Z,Lei T,Lu Ying Z,et al.The expression of proto-oncogene EIF4E in laryngeal squamous cell carcinoma[J].Laryngoscope,2003,113(7):1238-1243.
17 Liotta LA.Tumor invasion and metastases-role of the extracellular matrix:Rhoads Memorial Award lecture[J]Cancer Res,1986,46(1):1.
18 Chambers AF,Matrisian LM.Changing view of the role of matrix metalloproteinases in metastasis.J Natl Cancer Inst,1997,89(3):12-60.
19 戴纪刚.Ⅳ型胶原酶与肿瘤的浸润.国外医学生理病理科学与临床分册.2000,20(4):97-99.
20 Fang J,ShingY,Wiederschain D,et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor rnodel[J].Proc Natl Acad Sci USA,2000,97(8):38-84.
21 Spiridione G,Giorgio S,Laura M,et al.Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy.Cancer Res,1992,52(5):4548-4549.
22 Zunker S,Lysik RM,Zarrabi MH,et al.Mr 92 000 type Ⅳcollagease is increase in plasma of patients with colon cancer and breast cancer.Cancer Res,1993,53(2):140-143.
23 Zeng ZS,Ouillem.Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metallopro teinase 2 mRNA expression in human colorectal cancer and liver metastases.Br J Cancer,1995,72(4):575-579.
24 Naylor M S,Stamp GW,Davies BD,et al.Expression and activity of MMPs and their regulators in ovarian cancer.Int J Cancer,1994,58(5):50-54.
25 Passlick B,Sienel W,Seen-Hibler R,et al.Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early stage non-small cell lung cancer.Clin Cancer Res,2000,6(10):3944.
26 姚利,陆兴等.鼻咽癌间质微血管密度与MMP-2表达和肿瘤转移的关系.中国耳鼻咽喉头颈外科,2007,14(10):571-573.
27 邝国乾,陈龙,杨荣宁,等.鼻咽癌远处转移临床相关因素分析.实用癌症杂志.2002,17(1):57-59.
28 莫立根,邝国乾,张成,等.鼻咽癌局部扩散与远处转移的相关性.临床耳鼻咽喉科杂志.2005,19(20):926-928.
1 Wilkie AO,Patey SJ,Kan SH FGFs,their receptors,and human limb malformations:clinical and molecular correlations.Am J Med Genet,2002,12(3):266-278.
2 Okada-Ban.M,Thiery J P.Jouanneau J,et al.Fibroblast growth factor-2.Int Biochem,2000,32(3):263-267.
3 Sepp TT,liLl,Lee KH,et al.Basic fibroblast growth factor increase expression of the aββ integrin complex on humanm icrovascular endothelial cells[J].J Invest Dermatol,1994,103(3):295.
4 van-der-Meer W,Mackenzie MA.Dinnissen JWB,et al.Pseudoplatelet:a retrospective study of their incidence and interference with platelet counting.J Clin Pathol,2003.56(10):772-774.
5 Nomura S.Function and clinical significance of platelet-de-rived microparticles.Int J Hematol.2001,74(4):397-404.
6 Schulze-osthff K,Rissu W.Vollmer E,et al In site dection of basic Fibroblast growth factor by highly specilic an tibodies Am J Path,1990,137(4):85.
7 周廷冲.多肽生长因子基础与临床[M].北京:中国科学技术出版社.1992.9.
8 石歧兴,李方,刘同才,等.VEGF和bFGF共同表达与膀胱癌生物学行为的关系[J].实用肿瘤杂志,2001,16(1):30.
9 蔡欣然,黄长玉,杨发端,等.人肝胆管癌中碱性成纤维细胞生长因子及其受体的表达[J].中华实验外科杂志,2000,17(1):82.
10 邓志宏,黄维国,邱建华,等.喉粘膜癌前病变和癌变中VEGF、bFGF 和KGF的表达分析[J].肿瘤,1999,19(6):338.
11 胡波,贾永华,李小薇.碱性纤维母细胞生因子(bFGF)的检测有助于判断肉瘤恶性程度[J].大连医科大学学报,2001,23,(1):24.
12 林卫,彭芝兰.碱性成纤维细胞生长因子在卵巢上皮性肿瘤中的表达及意义[J].中国修复重建外科杂志,1999,13(5):299.
13 李玲,刘毅智,吴宜林,等.卵巢恶性肿瘤VEGF mRNA和bFGF mRNA 的表达及其意义[J].湖南医科大学学报,2000,25(4):406.
14 钟华,邓方明,孔祥田等.碱性成纤维细胞生长因子及其受体在肾癌组织中的表达[J].中华外科杂志,1996,34(11):651.
15 Takahashi K Mulliken JB.The cellular marks that distinguish the phase of hemmagioma during infancy and childhc[J].J Clin Invest,1994,93(2):23-64.
16 陈光,贺占国,王永海,等.毛细血管瘤组织中成纤维细胞生长因子(bFGF)的表达水平[J].临床口腔医学杂志,1997,13(3):147.
17 Schulze-osthff K,Rissu W.Vollmer E,et al In site dection of basic Fibroblast growth Factor by highly specilic an tibodies Am J Path,1990,137(4):85.
2 陈春燕,卢泰祥.局部晚期鼻咽癌治疗新进展.中国癌症杂志,2006,16(6):437-441.
3 曾益新,主编.肿瘤学[M].北京:人民卫生出版社,2001:177-179.
4 Harlozinska A.Progress in molecular mechanisms of tumor metastasis and angiogenesis[J].Anticancer Res,2005,25(5):3327-3333.
5 赵军,刘叙仪,张青云,等.晚期非小细胞肺癌患者外周血VEGF和bFGF及MMP-9水平与预后的关系[J].中华肿瘤杂志,2005,27(11):676-679.
6 郭新,李玉林,张丽红,等.胃癌组织碱性成纤维细胞生成因子表达及对血管新生和肿瘤进展的影响[J].中华消化杂志,2002:22(4):209-212.
7 陈洪雷,刁路明,刘铭球,等.MMP2、TIMP2、bFGF在大鼠肺鳞癌癌变过程中的动态表达.肿瘤,2002,22(5):375-378.
8 Wilkie AO,Patey SJ,Kan SH FGFs,their receptors,and human limb malformations:clinical and molecular correlations.Am J Med Genet,2002,12(3):266-278.
9 Abuhaibeid S,Czubayko F,Aiqner A.The fibroblast growth factor-binding protein FGF-BP[J].Int J Biochem Cell Biol, 2006,38(9):1463-1468.
10 Pallares J,Rojo F,Iriarte J,et al.Study of micmvessel density and the expression of the angiogenic factors VEGF,bFGF and the receptors Flt-1 and FLK-1 in benign,premalignant an d malignant prostate tissues[J].2006,21(8):857-865.
11 Frank Riedel,Karl Gotte,Wolfgang Bergler,et al.Expression fbasic fibroblast growth factor protein and its down-regulation by intelfemns in head and neck cancer[J].Head & Neck,2000,22(2):183-189.
12 Hase T,Kawashiri S,Tanaka A,et al.Correlation of basic fibroblast growth factor expression with the invasion and the prognosis of Oral squamous cell carcinoma[J].Oral Pathol Med,2006,35(3):136-139.
13 Veselv D,Am J,Matucha P,et al.Serum levels of angiogenic growth factors in patients with thyroid gland tumors and parathyroid adenoma[J].Neuro Endocrinol Lett,2003,24(6):417-419.
14 Homer JJ.Greenman J,Staford ND.Circulating angiogenic cyto'kines as tumour markers an d prognostic factors in head and neck squamous cell carcinoma[J].Clin Otolaryngol Allied Sci,2002,27(1):32-37.
15 Li C,Shintani S,Terakado N,et al.Micmvessel density and expression of vascular endothelial growth factor,basic fibmblast growth factor,and platelet-derived endothelial growth factor in oral squamous cell carcinomas[J].Int J Oral Maxillofac Surg,2005,34(5):559-565.
16 Liang Z,Lei T,Lu Ying Z,et al.The expression of proto-oncogene EIF4E in laryngeal squamous cell carcinoma[J].Laryngoscope,2003,113(7):1238-1243.
17 Liotta LA.Tumor invasion and metastases-role of the extracellular matrix:Rhoads Memorial Award lecture[J]Cancer Res,1986,46(1):1.
18 Chambers AF,Matrisian LM.Changing view of the role of matrix metalloproteinases in metastasis.J Natl Cancer Inst,1997,89(3):12-60.
19 戴纪刚.Ⅳ型胶原酶与肿瘤的浸润.国外医学生理病理科学与临床分册.2000,20(4):97-99.
20 Fang J,ShingY,Wiederschain D,et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor rnodel[J].Proc Natl Acad Sci USA,2000,97(8):38-84.
21 Spiridione G,Giorgio S,Laura M,et al.Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy.Cancer Res,1992,52(5):4548-4549.
22 Zunker S,Lysik RM,Zarrabi MH,et al.Mr 92 000 type Ⅳcollagease is increase in plasma of patients with colon cancer and breast cancer.Cancer Res,1993,53(2):140-143.
23 Zeng ZS,Ouillem.Distinct pattern of matrix metalloproteinase 9 and tissue inhibitor of metallopro teinase 2 mRNA expression in human colorectal cancer and liver metastases.Br J Cancer,1995,72(4):575-579.
24 Naylor M S,Stamp GW,Davies BD,et al.Expression and activity of MMPs and their regulators in ovarian cancer.Int J Cancer,1994,58(5):50-54.
25 Passlick B,Sienel W,Seen-Hibler R,et al.Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early stage non-small cell lung cancer.Clin Cancer Res,2000,6(10):3944.
26 姚利,陆兴等.鼻咽癌间质微血管密度与MMP-2表达和肿瘤转移的关系.中国耳鼻咽喉头颈外科,2007,14(10):571-573.
27 邝国乾,陈龙,杨荣宁,等.鼻咽癌远处转移临床相关因素分析.实用癌症杂志.2002,17(1):57-59.
28 莫立根,邝国乾,张成,等.鼻咽癌局部扩散与远处转移的相关性.临床耳鼻咽喉科杂志.2005,19(20):926-928.
1 Wilkie AO,Patey SJ,Kan SH FGFs,their receptors,and human limb malformations:clinical and molecular correlations.Am J Med Genet,2002,12(3):266-278.
2 Okada-Ban.M,Thiery J P.Jouanneau J,et al.Fibroblast growth factor-2.Int Biochem,2000,32(3):263-267.
3 Sepp TT,liLl,Lee KH,et al.Basic fibroblast growth factor increase expression of the aββ integrin complex on humanm icrovascular endothelial cells[J].J Invest Dermatol,1994,103(3):295.
4 van-der-Meer W,Mackenzie MA.Dinnissen JWB,et al.Pseudoplatelet:a retrospective study of their incidence and interference with platelet counting.J Clin Pathol,2003.56(10):772-774.
5 Nomura S.Function and clinical significance of platelet-de-rived microparticles.Int J Hematol.2001,74(4):397-404.
6 Schulze-osthff K,Rissu W.Vollmer E,et al In site dection of basic Fibroblast growth factor by highly specilic an tibodies Am J Path,1990,137(4):85.
7 周廷冲.多肽生长因子基础与临床[M].北京:中国科学技术出版社.1992.9.
8 石歧兴,李方,刘同才,等.VEGF和bFGF共同表达与膀胱癌生物学行为的关系[J].实用肿瘤杂志,2001,16(1):30.
9 蔡欣然,黄长玉,杨发端,等.人肝胆管癌中碱性成纤维细胞生长因子及其受体的表达[J].中华实验外科杂志,2000,17(1):82.
10 邓志宏,黄维国,邱建华,等.喉粘膜癌前病变和癌变中VEGF、bFGF 和KGF的表达分析[J].肿瘤,1999,19(6):338.
11 胡波,贾永华,李小薇.碱性纤维母细胞生因子(bFGF)的检测有助于判断肉瘤恶性程度[J].大连医科大学学报,2001,23,(1):24.
12 林卫,彭芝兰.碱性成纤维细胞生长因子在卵巢上皮性肿瘤中的表达及意义[J].中国修复重建外科杂志,1999,13(5):299.
13 李玲,刘毅智,吴宜林,等.卵巢恶性肿瘤VEGF mRNA和bFGF mRNA 的表达及其意义[J].湖南医科大学学报,2000,25(4):406.
14 钟华,邓方明,孔祥田等.碱性成纤维细胞生长因子及其受体在肾癌组织中的表达[J].中华外科杂志,1996,34(11):651.
15 Takahashi K Mulliken JB.The cellular marks that distinguish the phase of hemmagioma during infancy and childhc[J].J Clin Invest,1994,93(2):23-64.
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