细胞外基质蛋白1在分化型甲状腺癌的表达及其临床意义
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摘要
研究目的:
研究细胞外基质蛋白1(extracellular matrix protein 1,ECM1)在分化型甲状腺癌的mRNA和蛋白表达及其临床意义。
研究方法:
对31例分化型甲状腺癌手术标本,采用半定量RT-PCR和免疫组化技术分别检测癌组织和癌旁组织中ECM1的表达情况。
研究结果:
1.半定量RT-PCR: ECM1mRNA在分化型甲状腺癌癌组织中的相对表达量0.94±0.06,癌旁组织中为0.64±0.03,两者相比差异有统计学意义(t=30.194,P<0.01)。
2.免疫组化: ECM1主要分布在细胞质中,在细胞膜和细胞间也有少量表达。在分化型甲状腺癌癌组织的ECM1阳性表达率为64.51%,癌旁组织的阳性表达率为16.13%,两者相比差异有统计学意义( x 2=15.08,P<0.01)。
3.ECM1的表达与分化型甲状腺癌患者的性别、年龄、肿瘤大小、病理类型及临床分期无关(P>0.05),与淋巴结的转移有关(P<0.01)。
结论:
1.ECM1mRNA在癌组织的相对表达量高于癌旁组织;
2. ECM1蛋白在癌组织的相对表达量高于癌旁组织;
3.ECM1的表达异常可能与分化型甲状腺癌的发生、发展有关,可能作为一种新的分子标记物在分化型甲状腺癌的诊断中起到一定的作用。
Objective:
To examine the expression of mRNA and protein of extracellular matrix protein 1(ECM1) in differentiated thyroid carcinoma.
Methods:
The expression level of ECM1 in the cancerous tissues and adjacent tissues around cancer(>2cm) in 31 samples of differentiated thyroid carcinoma was detected with RT-PCR and immunohistochemistry.
Results:
1.Semi-quantitative results of RT-PCR showed that the relative expression of ECM1mRNA was 0.94±0.06 in the cancerous tissues and 0.64±0.03 in the adjacent tissues, respectively. The difference was statistics significant(t=30.194,P<0.01).
2. The positive expression of ECM1 in the cancerous tissues was in 20 of 31 samples (64.51%); whereas in the adjacent tissues was 5 of 31 samples (16.13%). The difference was statistics significant(χ2=15.08, P<0.01).
3. No correlation was found between the expression of ECM1 and clinical date such as gender, age, tumor size, histology, TNM stage ( P>0.05), except metastasis of cervical lymph node(P<0.01).
Conclusions:
1. The expression level of ECM1 mRNA in the cancerous tissues is significant higher than in the adjacent tissues.
2. The expression level of ECM1 protein in the cancerous tissues is significant higher than in the adjacent tissues.
3. Over-expression of ECM1 is associated with the carcinogenesis of differentiated thyroid carcinoma, and may become a mark to detect the tumor.
研究细胞外基质蛋白1(extracellular matrix protein 1,ECM1)在分化型甲状腺癌的mRNA和蛋白表达及其临床意义。
研究方法:
对31例分化型甲状腺癌手术标本,采用半定量RT-PCR和免疫组化技术分别检测癌组织和癌旁组织中ECM1的表达情况。
研究结果:
1.半定量RT-PCR: ECM1mRNA在分化型甲状腺癌癌组织中的相对表达量0.94±0.06,癌旁组织中为0.64±0.03,两者相比差异有统计学意义(t=30.194,P<0.01)。
2.免疫组化: ECM1主要分布在细胞质中,在细胞膜和细胞间也有少量表达。在分化型甲状腺癌癌组织的ECM1阳性表达率为64.51%,癌旁组织的阳性表达率为16.13%,两者相比差异有统计学意义( x 2=15.08,P<0.01)。
3.ECM1的表达与分化型甲状腺癌患者的性别、年龄、肿瘤大小、病理类型及临床分期无关(P>0.05),与淋巴结的转移有关(P<0.01)。
结论:
1.ECM1mRNA在癌组织的相对表达量高于癌旁组织;
2. ECM1蛋白在癌组织的相对表达量高于癌旁组织;
3.ECM1的表达异常可能与分化型甲状腺癌的发生、发展有关,可能作为一种新的分子标记物在分化型甲状腺癌的诊断中起到一定的作用。
Objective:
To examine the expression of mRNA and protein of extracellular matrix protein 1(ECM1) in differentiated thyroid carcinoma.
Methods:
The expression level of ECM1 in the cancerous tissues and adjacent tissues around cancer(>2cm) in 31 samples of differentiated thyroid carcinoma was detected with RT-PCR and immunohistochemistry.
Results:
1.Semi-quantitative results of RT-PCR showed that the relative expression of ECM1mRNA was 0.94±0.06 in the cancerous tissues and 0.64±0.03 in the adjacent tissues, respectively. The difference was statistics significant(t=30.194,P<0.01).
2. The positive expression of ECM1 in the cancerous tissues was in 20 of 31 samples (64.51%); whereas in the adjacent tissues was 5 of 31 samples (16.13%). The difference was statistics significant(χ2=15.08, P<0.01).
3. No correlation was found between the expression of ECM1 and clinical date such as gender, age, tumor size, histology, TNM stage ( P>0.05), except metastasis of cervical lymph node(P<0.01).
Conclusions:
1. The expression level of ECM1 mRNA in the cancerous tissues is significant higher than in the adjacent tissues.
2. The expression level of ECM1 protein in the cancerous tissues is significant higher than in the adjacent tissues.
3. Over-expression of ECM1 is associated with the carcinogenesis of differentiated thyroid carcinoma, and may become a mark to detect the tumor.
引文
1. 许 晨 , 赵 文 川 . 甲 状 腺 癌 分 子 标 记 物 研 究 进 展 . 现 代 肿 瘤 医 学 [J]. 2006,14(3) :357-360
2. 李 风 和 , 俞 光 岩 . 细 胞 外 基 质 与 肿 瘤 转 移 . 现 代 口 腔 医 学 杂 志[J].2000,14(3):206-207.
3.韩韬,段国兰.细胞外基质与肿瘤转移关系的研究进展.医学综述,2000,8(1):22-24.
4. Mathieu E, Meheμs L,Raymakers J,et al. Characterization of the osteogenic stromal cell line MN7: identification of secreted MN7 proteins μsing twodimensional polyacrylamide gel electrophoresis, western blotting and microseqμencing. J. Bone Miner. Res, 1994(9):903-913
5. Patrick Smits,Jian Ni,Ping Peng,et al. The hμman extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern,and chromosomal localization. J.Genomics,1997,45(3):487-495.
6. Maurizio Mongiat, Jian Fu,Rachel Oldershaw,et al.Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis.J. Biol Chem,2003 ,78(19):17491-17499
7. Deckers M,Smits P,Karperien M,et al.Recombinant human extracellular matrix protein 1 inhibit alkaline phosphatase activity and mineralizztion of mouse embryonic metatarsals in vitro. J.Bone, 2001 28(1):14-20
8. Hamada T,Mclean WH,Ramsay M,et al.Lipoid proteinosis maps to 1q21 and is caused by mutation in the extracellar matrix protein 1 gene(ECM). J.Hum Mol Genet, 2002,11(7):833-840
9. TaskerGL , WojnarowskaF.Lichen selerosus.Clin Exp Dermatol , 2003 ,28:128-133.
10. Han Z, Ni J, Smits P, et al. Extracellular matrix protein 1 (ECM1) hasangiogenic properties and is expressed by breast tumor cells. J.FASEB ,2001,15(6), 988-994
11.Wang L, Yu J,Ni J, et al. Extracellular matrix protein 1(ECM1) is over-expres sed in malignant epithelial tumors . J.Cancer Lett,2003,200(1):57-67
12. 侯彦强,范列英,屠小卿,等. 细胞外基质蛋白 1 在肿瘤中的表达及意义[J]. 第二军医大学学报 , 2004,25(12)1314-1316 .
13. Pauws E,Veenboer GJ,Smit JW,et al.Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles. J.FASEB J.2004,18(3):560-561
14. Kebebew E,Peng M, Reiff E,et al. ECM1 and TMPRSS4 are diagnos tic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. J. AnnSurg, 2005,242(3):353-363
15.韩朝,林国经,黄建民,等.细胞外基质蛋白- 1 与喉癌血管生成和转移的关系[J].临床耳鼻喉科杂志,2006,20(3):116-118
16.熊瑞. 甲状腺癌的治疗进展. 临床医学[J]. 2007,27(9) 88-89
17.徐从高,张茂宏,杨兴季,等译.癌--肿瘤学原理和实践.第 5 版.济南:山东科学技术出版社,2001.83～160.
18. Folkman J.Tumor angiogenesis:therapeutic implications. J.N Engl J Med.1971,285:1182-1186.
19. Yang F,Brune J,Naylor S,et al..Human group-specific component(GC)is a member of the albumin family. J.Proc.Natl.Acad.Sci.USA ,1985,82(23): 7994-7998.
20. Soltysik-Espanola M,Kinzing DC,Pfarr K, et al. Endo16, a large multidomain protein found on the surface and ECM of endodermal cells during sea urchin gastrulation, binds calcium. J. Der.Biol,1994,165(1),73-85
21.Iwasaka C,Tanaka K,Abe M,et al. Ets-1 regulates angiogenesis by inducing the expression of urokiase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells.J.Cell. Physiol, 1996,169(3):522-531
22. Marenholz I,Volz A,Ziegler A,et al. Genetic analysis of the epidermal differentiation complex(EDC)on human chromosome 1q21:Chromosomal orientation,newmarkers,and a 6-Mb YAC contig. J.Genomics, 1996,37:295-302
23. 胡振富,高建华,李薇,等.病理性瘢痕中 S100 蛋白基因的差异表达[J].中国临床康复,2006,10(32):86-88
1.Mathieu E, Meheus L,Raymakers J,et al. Characterization of the osteogenic stromal cell line MN7: identification of secreted MN7 proteins using twodimensional polyacrylamide gel electrophoresis, western blotting and microsequencing. J. Bone Miner. Res, 1994(9)903-913
2. Patrick Smits,Jian Ni,Ping Peng,et al. The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern,and chromosomal localization. J.Genomics, 1997,45(3),487-495.
3.Marenholz I,Volz A,Ziegler A,et al. Genetic analysis of the epidermal differentiation complex(EDC)on human chromosome 1q21:Chromosomal orientation,newmarkers,and a 6-Mb YAC contig. J.Genomics, 1996,37:295-302.
4. Maurizio Mongiat, Jian Fu,Rachel Oldershaw,et al.Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis.J. Biol Chem, 2003 ,78(19):17491-17499
5.Yang F,Brune J,Naylor S,et al..Human group-specific component(GC)is a member of the albumin family. J.Proc.Natl.Acad.Sci.USA , 1985,82(23): 7994-7998.
6.Kragh-Hansen U..Structure and ligand binding properties of humanserum albumin. J.Danish Med.Bull, 1990,37:57-84.
7.Soltysik-Espanola M,Kinzing DC,Pfarr K, et al. Endo16, a large multidomain protein found on the surface and ECM of endodermal cells during sea urchin gastrulation, binds calcium. J. Der.Biol, 1994,165(1),73-85
8.Iwasaka C,Tanaka K,Abe M,et al. Ets-1 regulates angiogenesis by inducing the expression of urokiase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells.J.Cell. Physiol, 1996,169(3):522-531
9.胡振富,高建华,李薇,等.病理性瘢痕中 S100 蛋白基因的差异表达[J ].中国临床康复, 2006,10(32):86-88
10. Han Z, Ni J, Smits P, et al. Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells. J.FASEB , 2001,15(6), 988-994
11. Deckers M,Smits P,Karperien M,et al.Recombinant human extracellular matrix protein 1 inhibit alkaline phosphatase activity and mineralizztion of mouse embryonic metatarsals in vitro. J.Bone, 2001 28(1):14-20
12. Hamada T,Mclean WH,Ramsay M,et al.Lipoid proteinosis maps to 1q21 and is caused by mutation in the extracellar matrix protein 1 gene(ECM). J.Hum Mol Genet, 2002,11(7):833-40
13. Wang L, Yu J,Ni J, et al. Extracellular matrix protein 1(ECM1) is over-expres sed in malignant epithelial tumors . J.Cancer Lett, 2003,200(1):57-67
14. 侯彦强,范列英,屠小卿,等. 细胞外基质蛋白 1 在肿瘤中的表达及意义[J]. 第二军医大学学报 , 2004,25(12)1314-1316 .
15. Pauws E,Veenboer GJ,Smit JW,et al.Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles. J.FASEB J. 2004,18(3):560-561
16. Kebebew E,Peng M, Reiff E,et al. ECM1 and TMPRSS4 are diagnos tic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. J.AnnSurg, 2005,242(3):353-363
17.韩朝,林国经,黄建民,等.细胞外基质蛋白- 1 与喉癌血管生成和转移的关系[J].临床耳鼻喉科杂志, 2006,20(3):116-118
2. 李 风 和 , 俞 光 岩 . 细 胞 外 基 质 与 肿 瘤 转 移 . 现 代 口 腔 医 学 杂 志[J].2000,14(3):206-207.
3.韩韬,段国兰.细胞外基质与肿瘤转移关系的研究进展.医学综述,2000,8(1):22-24.
4. Mathieu E, Meheμs L,Raymakers J,et al. Characterization of the osteogenic stromal cell line MN7: identification of secreted MN7 proteins μsing twodimensional polyacrylamide gel electrophoresis, western blotting and microseqμencing. J. Bone Miner. Res, 1994(9):903-913
5. Patrick Smits,Jian Ni,Ping Peng,et al. The hμman extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern,and chromosomal localization. J.Genomics,1997,45(3):487-495.
6. Maurizio Mongiat, Jian Fu,Rachel Oldershaw,et al.Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis.J. Biol Chem,2003 ,78(19):17491-17499
7. Deckers M,Smits P,Karperien M,et al.Recombinant human extracellular matrix protein 1 inhibit alkaline phosphatase activity and mineralizztion of mouse embryonic metatarsals in vitro. J.Bone, 2001 28(1):14-20
8. Hamada T,Mclean WH,Ramsay M,et al.Lipoid proteinosis maps to 1q21 and is caused by mutation in the extracellar matrix protein 1 gene(ECM). J.Hum Mol Genet, 2002,11(7):833-840
9. TaskerGL , WojnarowskaF.Lichen selerosus.Clin Exp Dermatol , 2003 ,28:128-133.
10. Han Z, Ni J, Smits P, et al. Extracellular matrix protein 1 (ECM1) hasangiogenic properties and is expressed by breast tumor cells. J.FASEB ,2001,15(6), 988-994
11.Wang L, Yu J,Ni J, et al. Extracellular matrix protein 1(ECM1) is over-expres sed in malignant epithelial tumors . J.Cancer Lett,2003,200(1):57-67
12. 侯彦强,范列英,屠小卿,等. 细胞外基质蛋白 1 在肿瘤中的表达及意义[J]. 第二军医大学学报 , 2004,25(12)1314-1316 .
13. Pauws E,Veenboer GJ,Smit JW,et al.Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles. J.FASEB J.2004,18(3):560-561
14. Kebebew E,Peng M, Reiff E,et al. ECM1 and TMPRSS4 are diagnos tic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. J. AnnSurg, 2005,242(3):353-363
15.韩朝,林国经,黄建民,等.细胞外基质蛋白- 1 与喉癌血管生成和转移的关系[J].临床耳鼻喉科杂志,2006,20(3):116-118
16.熊瑞. 甲状腺癌的治疗进展. 临床医学[J]. 2007,27(9) 88-89
17.徐从高,张茂宏,杨兴季,等译.癌--肿瘤学原理和实践.第 5 版.济南:山东科学技术出版社,2001.83～160.
18. Folkman J.Tumor angiogenesis:therapeutic implications. J.N Engl J Med.1971,285:1182-1186.
19. Yang F,Brune J,Naylor S,et al..Human group-specific component(GC)is a member of the albumin family. J.Proc.Natl.Acad.Sci.USA ,1985,82(23): 7994-7998.
20. Soltysik-Espanola M,Kinzing DC,Pfarr K, et al. Endo16, a large multidomain protein found on the surface and ECM of endodermal cells during sea urchin gastrulation, binds calcium. J. Der.Biol,1994,165(1),73-85
21.Iwasaka C,Tanaka K,Abe M,et al. Ets-1 regulates angiogenesis by inducing the expression of urokiase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells.J.Cell. Physiol, 1996,169(3):522-531
22. Marenholz I,Volz A,Ziegler A,et al. Genetic analysis of the epidermal differentiation complex(EDC)on human chromosome 1q21:Chromosomal orientation,newmarkers,and a 6-Mb YAC contig. J.Genomics, 1996,37:295-302
23. 胡振富,高建华,李薇,等.病理性瘢痕中 S100 蛋白基因的差异表达[J].中国临床康复,2006,10(32):86-88
1.Mathieu E, Meheus L,Raymakers J,et al. Characterization of the osteogenic stromal cell line MN7: identification of secreted MN7 proteins using twodimensional polyacrylamide gel electrophoresis, western blotting and microsequencing. J. Bone Miner. Res, 1994(9)903-913
2. Patrick Smits,Jian Ni,Ping Peng,et al. The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern,and chromosomal localization. J.Genomics, 1997,45(3),487-495.
3.Marenholz I,Volz A,Ziegler A,et al. Genetic analysis of the epidermal differentiation complex(EDC)on human chromosome 1q21:Chromosomal orientation,newmarkers,and a 6-Mb YAC contig. J.Genomics, 1996,37:295-302.
4. Maurizio Mongiat, Jian Fu,Rachel Oldershaw,et al.Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis.J. Biol Chem, 2003 ,78(19):17491-17499
5.Yang F,Brune J,Naylor S,et al..Human group-specific component(GC)is a member of the albumin family. J.Proc.Natl.Acad.Sci.USA , 1985,82(23): 7994-7998.
6.Kragh-Hansen U..Structure and ligand binding properties of humanserum albumin. J.Danish Med.Bull, 1990,37:57-84.
7.Soltysik-Espanola M,Kinzing DC,Pfarr K, et al. Endo16, a large multidomain protein found on the surface and ECM of endodermal cells during sea urchin gastrulation, binds calcium. J. Der.Biol, 1994,165(1),73-85
8.Iwasaka C,Tanaka K,Abe M,et al. Ets-1 regulates angiogenesis by inducing the expression of urokiase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells.J.Cell. Physiol, 1996,169(3):522-531
9.胡振富,高建华,李薇,等.病理性瘢痕中 S100 蛋白基因的差异表达[J ].中国临床康复, 2006,10(32):86-88
10. Han Z, Ni J, Smits P, et al. Extracellular matrix protein 1 (ECM1) has angiogenic properties and is expressed by breast tumor cells. J.FASEB , 2001,15(6), 988-994
11. Deckers M,Smits P,Karperien M,et al.Recombinant human extracellular matrix protein 1 inhibit alkaline phosphatase activity and mineralizztion of mouse embryonic metatarsals in vitro. J.Bone, 2001 28(1):14-20
12. Hamada T,Mclean WH,Ramsay M,et al.Lipoid proteinosis maps to 1q21 and is caused by mutation in the extracellar matrix protein 1 gene(ECM). J.Hum Mol Genet, 2002,11(7):833-40
13. Wang L, Yu J,Ni J, et al. Extracellular matrix protein 1(ECM1) is over-expres sed in malignant epithelial tumors . J.Cancer Lett, 2003,200(1):57-67
14. 侯彦强,范列英,屠小卿,等. 细胞外基质蛋白 1 在肿瘤中的表达及意义[J]. 第二军医大学学报 , 2004,25(12)1314-1316 .
15. Pauws E,Veenboer GJ,Smit JW,et al.Genes differentially expressed in thyroid carcinoma identified by comparison of SAGE expression profiles. J.FASEB J. 2004,18(3):560-561
16. Kebebew E,Peng M, Reiff E,et al. ECM1 and TMPRSS4 are diagnos tic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy. J.AnnSurg, 2005,242(3):353-363
17.韩朝,林国经,黄建民,等.细胞外基质蛋白- 1 与喉癌血管生成和转移的关系[J].临床耳鼻喉科杂志, 2006,20(3):116-118