肺癌肿瘤抑制因子1基因甲基化和肺癌肿瘤抑制因子1蛋白在宫颈病变中的表达及意义  

Significance of TSLC1 gene methylation and TSLC1 protein expression in the progression of cervical lesions

作　　者：赵旭晔[1,2] 崔勇[3] 李亚玲[4] 梁帅[5] 张彦[1] 解立武[4] 夏志卿[6] 杜劲松[6] 魏林萍 李亚里[1] 

机构地区：[1]解放军总医院解放军医学院妇科二病区,北京100853 [2]山西省肿瘤医院乳腺二科,030006 [3]滨州医学院病理生理教研室 [4]山西省肿瘤医院病理科 [5]山西省肿瘤医院乳腺二科 [6]山西省肿瘤医院科教科 [7]长治和平医院病理科

出　　处：《中华肿瘤杂志》2015年第5期356-360,共5页Chinese Journal of Oncology

摘　　要：目的探讨肺癌肿瘤抑制因子1（TSLC1）基因甲基化、TSLC1蛋白表达和高危型人乳头瘤病毒（HR-HPV）感染在宫颈癌前病变及宫颈癌中的意义。方法收集2011年3月至2012年8月间收治的92例不同宫颈病变患者，经病理证实为正常宫颈10例，宫颈上皮内瘤变（CIN）I级26例，CINII级20例，CIN Ⅲ级15例，宫颈癌21例。用甲基化特异性聚合酶链反应法（MSP）检测不同宫颈病变组织中TSLC1基因甲基化状态，免疫组化法检测不同宫颈病变组织中TSLC1蛋白的表达，第二代杂交捕获试验（HC2）检测不同宫颈病变组织中HR-HPVDNA的表达。结果正常宫颈组织、CINI级、CINII级、CINⅢ级和宫颈癌组织中TSLC1基因甲基化阳性率分别为10．0％、30．8％、55．0％、60．0％和66．7％，差异有统计学意义（P=0．004）。正常宫颈组织、CINI级、CINII级、CINⅢ级和宫颈癌组织中TSLC1蛋白阳性率分别为100．0％、80-8％、65．0％、33．3％和23-8％，差异有统计学意义（P=0．004）。正常宫颈组织、CINI级、CINⅡ级、CINⅢ级和宫颈癌组织中HR-HPVDNA阳性率分别为30．0％、65．4％、70．0％、93．3％和95．2％，差异有统计学意义（P=0．001）。从CIN进展到浸润性宫颈癌，TSLC1基因甲基化、TSLC1蛋白表达与HR-HPV感染无关（均P〉0．05），TSLC1基因甲基化与TSLC1蛋白表达呈负相关（r=-0．674，P〈0．001）。结论TSLC1基因启动子甲基化可能是宫颈癌发生的早期事件，TSLC1基因有望成为宫颈癌发生早期的敏感标志物，用于宫颈肿瘤的早期诊断及预后分析。Objective To study the expression and significance of tumor suppressor in lung cancer 1 （TSLC1） gene methylation, the expression of TSLC1 protein in cervix cancer and precancerous lesions as well as their relationship with HR-HPV DNA infection. Methods The clinicopathological data of 92 cases of different cervical lesions during March 2011 to August 2012 treated in our hospital were collected. There were pathologically confirmed 10 cases of normal cervix, 26 cases of cervical intraepithelial neoplasia （CIN） I , 20 cases of CIN II, 15 cases of CIN Ⅲ, and 21 cases of cervical cancer. Methylation-specific polymerase chain reaction （MSP） was used to detect the TSLC1 gene methylation status in cervical lesions, immunohistochemistry （SP） was used to detect the expressions of TSLC1 protein in cervical lesions, and the second generation hybrid capture （HC2） method was used to detect the high-risk HPV in cervical lesions. Results The expression rate of TSLC1 gene methylation in normal cervical tissue, CIN I , CINⅡ , CIN Ⅲ and SCC were 10.0%, 30.8%, 55.0%, 60.0%, 66.7%, respectively, showing a statistically significant difference （P= 0.004）. The positive expression rate of TSLC1 protein in normal cervical tissue, CIN I , CIN Ⅱ, CINⅢ and SCC were 100.0%, 80.8%, 65.0%, 33.3%, and 23.8%, respectively, with a significant difference （P= 0.004）. In the progression from CIN to invasive cervical cancer, there was no significant correlation between TSLC1 gene methylation and HR-HPV DNA infection （P = 0.919）, TSLC1 protein expression and HR-HPV DNA infection （ P = 0.664）. The correlation analysis showed a negative correlation between TSLC1 gene methylation and TSLC1 protein expression （ r = - 0. 674, P 〈 0. 001 ）. Conclusions TSLC1 gene promoter methylation may be an early event in the cervical carcinogenesis, become an early sensitive marker, and serve the early prevention and prognostic prediction for cervical cancer.

关 键 词：宫颈肿瘤 宫颈上皮内瘤变 肺癌肿瘤抑制因子1 甲基化 诊断 预后 

分 类 号：R734.2[医药卫生—肿瘤]