转化生长因子β1在胃癌组织中的表达及其临床意义
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摘要
目的研究转化生长因子β1(Transforming Growth Factorβ1)在胃癌、胃不典型增生及正常胃组织中的表达及其与胃癌的发生、发展、侵袭及转移的关系。
方法采用免疫组织化学(immunohistochemistry,IHC)S-P法检测56例胃癌组织、30例胃不典型增生(轻-中度)组织和20例正常胃组织中的TGF-β1的表达水平,分析在胃癌发生、发展不同阶段TGF-β1表达变化及TGF-β1与胃癌患者临床病理特征之间的关系。应用SPSS16.0统计软件包,根据资料类型分别采用χ~2检验、非参数秩和检验进行统计学分析处理,检验显著性水准取P=0.05,以P<0.05为差异有统计学意义。
结果
1 TGF-β1阳性表达呈棕黄色颗粒,主要定位于细胞质,细胞核中偶见散在的表达。正常胃组织、胃不典型增生(轻-中度)组织和胃癌组织中TGF-β1的总阳性表达率分别是10%(2/20)、43.3%(13/30)、83.9%(47/56),差异有显著性意义(H =45.46,P<0.01)。
2 TGF-β1在胃癌分化程度较差组中的表达高于分化程度较好组中的表达,差异有统计学意义(u=-2.26,P=0.024),在浆膜浸润组中的表达高于无浆膜浸润组中的表达,差异有统计学意义(u=-3.47,P=0.001),在有淋巴结转移组中的表达明显高于无淋巴结转移组中的表达,差异有显著性意义(u=-3.87,P<0.001),在临床分期(TNM)为Ⅲ+Ⅳ期组中的表达高于Ⅰ+Ⅱ期组的表达,差异有统计学意义(u=-3.19,P=0.001);TGF-β1的表达与胃癌患者的性别、年龄及胃癌发生部位均无相关性(P>0.05)。
结论
1 TGF-β1可能在胃癌的发生和发展过程中起重要作用。
2 TGF-β1有可能作为胃癌前病变发展为胃癌的预警因子。
3 TGF-β1的表达与胃癌的恶性生物学行为有一定关系,TGF-β1可能成为评估胃癌预后的有效指标。
Objective To investigate the expression of Transforming Growth Factorβ1 (TGF-β1) in the gastric carcinoma,atypical hyperplasia (low-moderate) of gastric mucosa and normal gastric mucosa tissue and the role of TGF-β1 in the gastric carcinoma development,invasion and metastasis.
Methods The expression of TGF-β1 was measured by S-P method of immunohistochemical technique in 56 patients with gastric carcinoma,30 patients with atypical hyperplasia (low-moderate) of gastric mucosa and 20 normal gastric mucosa tissues.We investigated the changes of TGF-β1 expression in three groups and the ralationship between TGF-β1 and clinicopathological characteristics of gastric carcinoma;SPSS16.0 for windows software was used to analyse data.Difference of the data between groups was calculated byχ~2 test or nonparametric test. Significant level of test taking P=0.05,the significant difference was considered when P<0.05.
Results
1 The positive expression of TGF-β1 was brown granule, TGF-β1 was mainly expressed in cytoplasm,occasionally scattered expressed in nucleus.The positive rate of TGF-β1 expression increased significantly in gastric carcinoma tissues(83.9%) compared with that in atypical hyperplasia (low-moderate) of gastric mucosa tissues(43.3%) and that in normal gastric mucosa tissues,with a significant difference(H =45.46,P<0.01).
2 The expression of TGF-β1 in patients with poorly differentiated cancers was significantly higher than those in well differentiated cancers(u=-2.26,P=0.024);The expression of TGF-β1 in serosa invasion group was significantly higher than those in no serosa invasion group(u=-3.47,P=0.001); The expression of TGF-β1 in lymph nodes metastatic group was significantly higher than those in no lymph nodes metastatic group (u=-3.87,P < 0.001); The expression of TGF-β1 in clinical stageⅢ+Ⅳgroup was significantly higher than those in clinical stageⅠ+Ⅱgroup (u=-3.19,P=0.001).The expression of TGF-β1 had no correlation with sex,age and different part of gastric carcinomas(P>0.05).
Conclusions
1 TGF-β1 probably play an important role in the origin and delepoment of gastric cancer.
2 TGF-β1 as a possible precancerous lesion to gastric cancer warning factor.
3 The expression of TGF-β1 is closely correlated with the malignant biologic behavior of gastric carcinoma, TGF-β1 may become an effective clinic prognostic index of gastric carcinoma.
方法采用免疫组织化学(immunohistochemistry,IHC)S-P法检测56例胃癌组织、30例胃不典型增生(轻-中度)组织和20例正常胃组织中的TGF-β1的表达水平,分析在胃癌发生、发展不同阶段TGF-β1表达变化及TGF-β1与胃癌患者临床病理特征之间的关系。应用SPSS16.0统计软件包,根据资料类型分别采用χ~2检验、非参数秩和检验进行统计学分析处理,检验显著性水准取P=0.05,以P<0.05为差异有统计学意义。
结果
1 TGF-β1阳性表达呈棕黄色颗粒,主要定位于细胞质,细胞核中偶见散在的表达。正常胃组织、胃不典型增生(轻-中度)组织和胃癌组织中TGF-β1的总阳性表达率分别是10%(2/20)、43.3%(13/30)、83.9%(47/56),差异有显著性意义(H =45.46,P<0.01)。
2 TGF-β1在胃癌分化程度较差组中的表达高于分化程度较好组中的表达,差异有统计学意义(u=-2.26,P=0.024),在浆膜浸润组中的表达高于无浆膜浸润组中的表达,差异有统计学意义(u=-3.47,P=0.001),在有淋巴结转移组中的表达明显高于无淋巴结转移组中的表达,差异有显著性意义(u=-3.87,P<0.001),在临床分期(TNM)为Ⅲ+Ⅳ期组中的表达高于Ⅰ+Ⅱ期组的表达,差异有统计学意义(u=-3.19,P=0.001);TGF-β1的表达与胃癌患者的性别、年龄及胃癌发生部位均无相关性(P>0.05)。
结论
1 TGF-β1可能在胃癌的发生和发展过程中起重要作用。
2 TGF-β1有可能作为胃癌前病变发展为胃癌的预警因子。
3 TGF-β1的表达与胃癌的恶性生物学行为有一定关系,TGF-β1可能成为评估胃癌预后的有效指标。
Objective To investigate the expression of Transforming Growth Factorβ1 (TGF-β1) in the gastric carcinoma,atypical hyperplasia (low-moderate) of gastric mucosa and normal gastric mucosa tissue and the role of TGF-β1 in the gastric carcinoma development,invasion and metastasis.
Methods The expression of TGF-β1 was measured by S-P method of immunohistochemical technique in 56 patients with gastric carcinoma,30 patients with atypical hyperplasia (low-moderate) of gastric mucosa and 20 normal gastric mucosa tissues.We investigated the changes of TGF-β1 expression in three groups and the ralationship between TGF-β1 and clinicopathological characteristics of gastric carcinoma;SPSS16.0 for windows software was used to analyse data.Difference of the data between groups was calculated byχ~2 test or nonparametric test. Significant level of test taking P=0.05,the significant difference was considered when P<0.05.
Results
1 The positive expression of TGF-β1 was brown granule, TGF-β1 was mainly expressed in cytoplasm,occasionally scattered expressed in nucleus.The positive rate of TGF-β1 expression increased significantly in gastric carcinoma tissues(83.9%) compared with that in atypical hyperplasia (low-moderate) of gastric mucosa tissues(43.3%) and that in normal gastric mucosa tissues,with a significant difference(H =45.46,P<0.01).
2 The expression of TGF-β1 in patients with poorly differentiated cancers was significantly higher than those in well differentiated cancers(u=-2.26,P=0.024);The expression of TGF-β1 in serosa invasion group was significantly higher than those in no serosa invasion group(u=-3.47,P=0.001); The expression of TGF-β1 in lymph nodes metastatic group was significantly higher than those in no lymph nodes metastatic group (u=-3.87,P < 0.001); The expression of TGF-β1 in clinical stageⅢ+Ⅳgroup was significantly higher than those in clinical stageⅠ+Ⅱgroup (u=-3.19,P=0.001).The expression of TGF-β1 had no correlation with sex,age and different part of gastric carcinomas(P>0.05).
Conclusions
1 TGF-β1 probably play an important role in the origin and delepoment of gastric cancer.
2 TGF-β1 as a possible precancerous lesion to gastric cancer warning factor.
3 The expression of TGF-β1 is closely correlated with the malignant biologic behavior of gastric carcinoma, TGF-β1 may become an effective clinic prognostic index of gastric carcinoma.
引文
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[8]吕有勇.多基因变异与胃黏膜癌变的关系.中华消化杂志,1996,16:9-1
[9]Derynck R,Akhurst R J,Balmain A.TGF-beta signaling in tumor suppression and cancer progression.Nat Genet,2001,29(2):117-129.
[10] Dunning A M,Ellis P D,McBride S,et a1.A transforming growth factor betal signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer.Cancer Res,2003,63(10):2610-2615.
[11] Li T, Cao BW, Dai Y,et al. Correlation of transforming growth factor beta-1 gene polymorphism C-509T and T869C and the risk of gastric cancer in China. J Gastroenterol Hepatol. 2008,23(4):638-42.
[12]Akhurst RJ.TGF-beta antagonists:Why suppress tumor suppressor.J Clin Invest,2002,109(12):1533-1536
[13] Blobe GC,Scheiemann WP,Lodish HF.Role of transforming growth factor beta in humandisease.New England J Med,2000,342(18):1350-1358
[14]庄则豪,陈玉丽,王承党,等.TGF-β1及TGF-β1受体在胃癌及癌前病变中的表达.世界华人消化杂志,1999,7(6):507-509
[15]王洪涛,李珍杰.TGF-beta1与Smad4与胃癌关系的研究.医学论坛杂志.2009,3(020):22-24
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[20]李荣,宋政军等.iNOS、TGFβ1、VEGF在胃癌中的表达及意义.现代肿瘤医学,2005,13(5):609-611.
[21]许洪卫,王龙,童晓晨,等.转化生长因子β1及其受体与胃癌侵袭性的关系.第二军医大学学报,2004,25(10):1149-1150
[22]粟美栖等.血清CA19-9、CEA、TGF-β1及VEGF检测在胃癌患者诊治中的意义.医学临床研究,2008, 25(8).
[23] Guo RF, Zang SZ, Zhang L, et a1.Relations of transforming growth factor-beta1 expression to differentiation and prognosis of advanced gastric cancer. Zhonghua Yi Xue Za Zhi 2006;86(46):3249-3254.
[24] Helmy A,Hammam OA, MD, The Role of TGF-beta-1 Protein and TGF-beta-1 Receptor in Immune Escape Mechanism in Bladder Cancer.MedGenMed. 2007;9(4):34.
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[40] Choi YH,Choi KC,Park YE,et al.Relationship of transforming growth factor beta 1 to angiogenesis in gastric carcinoma.J Korean Med Sci,1997,12(5):427-432.
[41]李荣,宋政军等.iNOS、TGFβ1、VEGF在胃癌中的表达及意义.现代肿瘤医学,2005,13(5):609-611.
[42]许洪卫,王龙,童晓晨,等.转化生长因子β1及其受体与胃癌侵袭性的关系.第二军医大学学报,2004,25(10):1149-1150
[43]粟美栖等.血清CA19-9、CEA、TGF-β1及VEGF检测在胃癌患者诊治中的意义.医学临床研究,2008, 25(8).
[44] Helmy A,Hammam OA, MD, The Role of TGF-beta-1 Protein and TGF-beta-1 Receptor in Immune Escape Mechanism in Bladder Cancer.MedGenMed. 2007;9(4):34.
[45] Guo RF, Zang SZ, Zhang L,et al. Relations of transforming growth factor-beta1 expression to differentiation and prognosis of advanced gastric cancer. Zhonghua Yi Xue Za Zhi. 2006;86(46):3249-54
[2] Parkin DM.Global cancer statistics in the the year 2000.Lancet Oncol 2001;2:533-543
[3] Massague J.TGF-βsignal transduction.Annu Rev Biochem,1998,67:753-91.
[4] Hata A. TGF-βsignal and cancer.Experimental Cell Research,2001,264:111-116.
[5] Vagenas K, Spyropoulos C, Gavala V,et al. TGFbeta1, TGFbeta2, and TGFbeta3 protein expression in gastric carcinomas: correlation with prognostics factors and patient survival. J Surg Res,2007,139(2):182-188
[6] Ebert MPA.Yu J,Miehlke S,et a1.Expression of transforming growth factor beta-1 in gastric cancer and in the gastric mucosa of first-degree relatives of patients with gastric cancer.Br J Cancer,2000,82:1795-1800.
[7]宋国庆,王强.RECK,MMP-9及TGF-β1在胃癌组织中的表达及其相互关系.世界华人消化杂志,2007,15(15):1731-1737.
[8]吕有勇.多基因变异与胃黏膜癌变的关系.中华消化杂志,1996,16:9-1
[9]Derynck R,Akhurst R J,Balmain A.TGF-beta signaling in tumor suppression and cancer progression.Nat Genet,2001,29(2):117-129.
[10] Dunning A M,Ellis P D,McBride S,et a1.A transforming growth factor betal signal peptide variant increases secretion in vitro and is associated with increased incidence of invasive breast cancer.Cancer Res,2003,63(10):2610-2615.
[11] Li T, Cao BW, Dai Y,et al. Correlation of transforming growth factor beta-1 gene polymorphism C-509T and T869C and the risk of gastric cancer in China. J Gastroenterol Hepatol. 2008,23(4):638-42.
[12]Akhurst RJ.TGF-beta antagonists:Why suppress tumor suppressor.J Clin Invest,2002,109(12):1533-1536
[13] Blobe GC,Scheiemann WP,Lodish HF.Role of transforming growth factor beta in humandisease.New England J Med,2000,342(18):1350-1358
[14]庄则豪,陈玉丽,王承党,等.TGF-β1及TGF-β1受体在胃癌及癌前病变中的表达.世界华人消化杂志,1999,7(6):507-509
[15]王洪涛,李珍杰.TGF-beta1与Smad4与胃癌关系的研究.医学论坛杂志.2009,3(020):22-24
[16] Ura H,Obara T,Yokota K,et al.Effects of transforming growth factor-beta released from gastric carcinoma cells on the contraction of collagen-matrix gels containing fibroblasts.Cancer Res. 1991, 51(13):3550-3554
[17]韩传吉.胃癌细胞周期异常与TGF-β信号转导的关系.山东大学硕士学位论文.2007
[18] Fu H,Hu Z,Wen J,et al.TGF-beta promotes invasion and metastasis of gastric cancer cells by increasing fascin1 expression via ERK and JNK signal pathways.Acta Biochim Biophys Sin,2009,41(8):648-656. [19 ] Choi YH,Choi KC,Park YE,et al.Relationship of transforming growth factor beta 1 to angiogenesis in gastric carcinoma.J Korean Med Sci,1997,12(5):427-432.
[20]李荣,宋政军等.iNOS、TGFβ1、VEGF在胃癌中的表达及意义.现代肿瘤医学,2005,13(5):609-611.
[21]许洪卫,王龙,童晓晨,等.转化生长因子β1及其受体与胃癌侵袭性的关系.第二军医大学学报,2004,25(10):1149-1150
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