宫颈鳞癌与转化生长因子β1的表达及人类乳头瘤病毒16 E6基因多态性的关系

J4 ›› 2012, Vol. 38 ›› Issue (4): 750-754.

宫颈鳞癌与转化生长因子β1的表达及人类乳头瘤病毒16 E6基因多态性的关系

王慧燕¹|蔡红兵²|陈长春²|王景²

1.武汉理工大学医院|湖北武汉　430070；2.武汉大学中南医院肿瘤生物学行为湖北省重点实验室湖北省肿瘤医学临床研究中心|湖北　武汉　430077

收稿日期:2012-03-07 出版日期:2012-07-28 发布日期:2012-07-28
通讯作者: 蔡红兵（Tel：027-67812648，E-mail：chb2105@163.com） E-mail:chb2105@163.com
作者简介:王慧燕（1969-）|女|江苏省无锡市人|副主任医师|医学硕士|主要从事妇科肿瘤的临床研究。
基金资助:
湖北省科技厅自然科学基金资助课题（2007ABA056）；湖北省卫生厅重点项目资助课题（JX3A17）

Relationships between TGF-β1 expression|HPV16 E6 gene polymorphism and squamous cervical carcinoma

WANG Hui-yan¹, CAI Hong-bing², CHEN Chang-chun², WANG Jing²

1. Hospital of |Wuhan University of Technology, Wuhan 430070, China；2. Zhongnan Hospital of Wuhan University, Key Laboratory of Tumor Biological Behaviors of HubeiProvince, Hubei Cancer Clinical Study Center|Wuhan 430071, China

Received:2012-03-07 Online:2012-07-28 Published:2012-07-28

摘要/Abstract

摘要：

［摘要］目的：探讨转化生长因子β1（TGF-β1）表达及人乳头瘤病毒（HPV）16 E6基因突变与宫颈癌发生发展的关系，阐明TGF-β1在宫颈癌发生中的作用机制。方法：收集2007年5月—2009年1月住院手术患者的新鲜宫颈组织，分为宫颈上皮内瘤变（CIN）Ⅰ级17例、CINⅡ-Ⅲ级17例及宫颈鳞状细胞癌39例，用免疫组织化学法检测组织标本中TGF-β1蛋白表达，用PCR法及直接测序检测组织HPV16 E6基因，分析其与宫颈癌发生发展的相关性。结果:CIN Ⅰ、CINⅡ-Ⅲ及宫颈鳞癌组织中TGF-β1的阳性率分别为 11.8%、35.3%及64.3%，其阳性率比较差异有统计学意义（P<0.01）。晚期宫颈鳞癌（ⅡB-Ⅳ期）患者TGF-β1表达率为88.9%，显著高于早期宫颈鳞癌（ⅠB-ⅡA）患者（76.7%）（P<0.01）。HPV16　E6在CIN Ⅰ、CINⅡ-Ⅲ组和宫颈鳞癌组织中的检出率分别为11.8%、41.2%和82.1%，其检出率组间比较差异有统计学意义(P<0.01)。HPV16 E6的阳性率与宫颈病变的进展程度呈正相关（r=0.592，P=0.001）。经基因测序，用DNAman软件对测序结果进行比对分析显示，共14例与标准株序列相同，最常见的突变位点是D25E，检出率为42.5%。HPV16 E6为非突变型患者中，其TGF-β1阳性率为50.0%；而在HPV16 E6D25E患者中，其TGF-β1阳性率为92.9%（P<0.05）。结论:TGF-β1 的表达与宫颈鳞癌的发生发展有关，HPV16 E6多态性可能与TGF-β1促进癌细胞的生长及侵袭有关。

关键词: 宫颈肿瘤；转化生长因子；人类乳头瘤病毒；E6基因；基因多态性；聚合酶链反应

Abstract:

Abstract:Objective To investigate the relationships between transforming growth factor beta 1(TGF-β1), polymorphism of human papilloma virus( HPV16) E6 gene and cervical carcinoma, and to clarify the possible mechanism of TGF-β1 in cervical carcinoma. Methods Fresh cervical tissues of hospitalized surgical patients between May 2007 to January 2009 were collected and divided into three groups, 17 cases of cervical intraepithelial neoplasia Ⅰ(CIN Ⅰ);17 cases of CIN Ⅱ-Ⅲ;39 cases of cervical squamous cell carcinoma. The immunohistochemical method was used to observe the TGF-β1 protein expression in cervical tissues,and the direct PCR method was performed to test the genotype of HPV16 E6, finally the relationships between them and the occurrence and development of cervical carcinoma were analyzed. Results The positive rates of TGF-β1 in CIN,CINⅡ-Ⅲ and cervical squamous cell carcinoma group were 11.8% ,35.3% and 64.3%, respectively, and there were significant differences between various groups (P<0.01 ).The expression of TGF-β1 in cervical carcinoma patients of stage ⅡB to ⅣA (88.9%) were significantly higher than that of stage ⅠB and ⅡA（76.7%）(P<0.01). The detection rates of HPV16　E6 in CINⅠ, CINⅡ-Ⅲ and cervical squamous cell carcioma group were 11.8%, 41.2% and 82.1%,there were significant differences between various groups(P<0.01). The positive rate of HPV16 E6 gene was positively related with the development of cervical carcinoma （r=0.592 ，P=0.001). By DNA sequencing, DNAman program was used to analyze the data, totally 14 sequences were the same as the standard strain，and the most common mutant site was D25E（42.5%). The TGF-β1 positive rates in HPV16 E6 non-mutant patients and in HPV16E6 D25E patients were 50.0% and 92.9%, respectively (P<0.05).Conclusion The occurrence and development of cervical carcinoma has something to do with TGF-β1 expression, and the HPV16　E6 polymorphism may be associated with the TGF-β1 which promote to growth and invasion of cancer.

Key words: uterine cervical neoplasms;transforming growth factor;human papilloma virus;E6 gene;gene polymorphism;polymerase chain reaction

中图分类号:

R737.33

王慧燕|蔡红兵|陈长春|王景. 宫颈鳞癌与转化生长因子β1的表达及人类乳头瘤病毒16 E6基因多态性的关系[J]. J4, 2012, 38(4): 750-754.

WANG Hui-yan, CAI Hong-bing, CHEN Chang-chun, WANG Jing. Relationships between TGF-β1 expression|HPV16 E6 gene polymorphism and squamous cervical carcinoma[J]. J4, 2012, 38(4): 750-754.

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