维吾尔族女性宫颈癌及上皮内瘤变中死亡相关蛋白激酶启动子（DAPK）高甲基化情况

[Death-associated protein kinase promoter (DAPK) hypermethylation in uterine cervical cancer and intraepithelial neoplasia in Uyghur nationality women].

作者信息

Niyazi Mayinuer, Liu Xiao-wan, Zhu Kai-chun

机构信息

Department of Gynecology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2012 Jan;34(1):31-4.

PMID:22490852

Abstract

OBJECTIVE

To investigate the methylation levels of death-associated protein kinase (DAPK) in Uyghur female patients with different cervical lesions in Xinjiang, and to discuss the relationship of the expression and significance of DAPK in normal cervix, chronic cervicitis, cervical intraepithelial neoplasia (CINI, CIN II/III) and invasive cervical squamous cell carcinoma.

METHODS

30 cases of normal cervix and chronic cervicitis, 30 cases of CINI, 30 cases of CINII/III and 30 cases of cervical squamous cell carcinoma were tested by methylation specific PCR (MSP). Expressions of DAPK in 30 cases of normal cervix and chronic cervicitis, 30 cases of CINI, 30 cases of CINII/III and 30 cases of cervical squamous cell carcinoma were assayed using immunohistochemical SP staining.

RESULTS

The methylation rate of DAPK gene in normal cervix and chronic cervicitis was 3.33%, 10% in cervical intraepithelial neoplasia CINI, 36.7% in CINII/III, and 63.3% in invasive cervical squamous cell carcinoma. The methylation rate of DAPK in the SCC group was significantly higher than that in the other groups (P < 0.05). Aberrant promoter methylation of the DAPK gene was positively correlated with the degree of cervical lesions. The positive rate of DAPK protein in normal cervix and chronic cervicitis was 93.3%, 83.3% in cervical intraepithelial neoplasia CINI, 60.0% in CINII/III, and 33.3% in invasive cervical squamous cell carcinoma. The expression of DAPK in the SCC group was significantly lower than that in the other groups (P < 0.05). The positive rate of DAPK protein was negatively correlated with the degree of cervical lesions (r(s) = -0.603, P < 0.001).

CONCLUSIONS

Methylation of DAPK is involved in the cervical carcinogenesis and DAPK gene promoter methylation occurs in the early development of cervical cancer in Uyghur women in Xinjiang. Detection of DAPK gene methylation may provide a basis for use in early detection of cervical cancer. DAPK protein expression is decreasing even disappears along with the progression of cervical lesions.

摘要

目的

探讨新疆维吾尔族女性不同宫颈病变中死亡相关蛋白激酶（DAPK）的甲基化水平，探讨DAPK在正常宫颈、慢性宫颈炎、宫颈上皮内瘤变（CINI、CIN II/III）及宫颈浸润性鳞状细胞癌中的表达及其意义。

方法

采用甲基化特异性PCR（MSP）检测30例正常宫颈及慢性宫颈炎、30例CINI、30例CINII/III及30例宫颈鳞状细胞癌组织。采用免疫组织化学SP染色法检测30例正常宫颈及慢性宫颈炎、30例CINI、30例CINII/III及30例宫颈鳞状细胞癌组织中DAPK的表达。

结果

正常宫颈及慢性宫颈炎组织中DAPK基因甲基化率为3.33%，宫颈上皮内瘤变CINI中为10%，CINII/III中为36.7%，宫颈浸润性鳞状细胞癌中为63.3%。SCC组DAPK甲基化率显著高于其他组（P<0.05）。DAPK基因启动子异常甲基化与宫颈病变程度呈正相关。正常宫颈及慢性宫颈炎组织中DAPK蛋白阳性率为93.3%，宫颈上皮内瘤变CINI中为83.3%，CINII/III中为60.0%，宫颈浸润性鳞状细胞癌中为33.3%。SCC组DAPK表达显著低于其他组（P<0.05）。DAPK蛋白阳性率与宫颈病变程度呈负相关（r(s)=-0.603，P<0.001）。