DNA甲基转移酶在宫颈癌组织中的表达及其与HPV的相关性分析

Expression of DNA methyltransferases in cervical cancer tissue and its relationship with HPV infection

目的探讨5种DNA甲基转移酶(DNMTs)在宫颈癌组织中的表达情况及其与高危型人乳头瘤病毒(HPV)感染的关系。方法应用荧光定量PCR、Western blotting、免疫组化检测40例宫颈癌组织、对应癌旁组织及20例正常宫颈组织中DNMT1、DNMT2、DNMT3a、DNMT3b和DNMT3l的表达情况,应用质谱法检测HPV感染情况。结果宫颈癌组织中DNMT1、DNMT3a、DNMT3b、DNMT3l的阳性表达率分别为90.0%、85.0%、70.0%、80.0%,在癌旁组织内的阳性表达率分别为87.5%、85.0%、72.5%、77.5%,均明显高于正常宫颈组织内的阳性表达率(分别为25.0%、15.0%、20.0%和30.0%),而DNMT2在宫颈癌和癌旁组织中阳性表达率仅为12.5%和17.5%,明显低于正常宫颈组织(约85.0%),且DNMT1、DNMT3a、DNMT3b与HPV阳性呈显著正相关(r值分别为0.709、0.538和0.536,P<0.05)。结论宫颈癌组织中DNMT的表达谱发生明显改变,且HPV高危亚型感染与DNMT1、DNMT3a、DNMT3b的表达升高密切相关。

Objective To investigate the expression situation of 5 kinds of DNA methyltransferases （DNMTs） in human cer- vical cancer tissues and its relationship with high risk-human papillomavirus（HR-HPV） infection. Methods The mRNA expres- sions of DNMT1 ,DNMT2,DNMT3a,DNMT3b and DNMT31 were detected in 20 cases of cervical cancer specimen and 20 cases of normal cervical tissues by real-time quantitative PCR, the protein expressions were detected by immunohistochemistry and Western blot. The HPV infection was detected by the mass spectrography. The results and clinical pathological parameters were analyzed. Results The positive expression rates of DNMT1, DNMT3a, DNMT3b and DNMT31 in cervical cancer tissues were 90. 0%, 85.0% ,70.0% and 80.0% respectively. The positive expression rates of DNMT1 ,DNMT3a,DNMT3b and DNMT31 in paracarcin- omous tissues were 87.5% ,85.0% ,72.5% and 77.5% respectively. All of them were significantly higher than those in the normal cervical tissues （25.0 %, 15.0 %, 20.0 % and 30.0 % ）. However, the positive expression rate of DNMT2 was 12.5 % in the cervical cancer tissues and 17. 5% in the paracarcinomous tissues, which were significantly lower than that in normal cervical tissues （85.0%）. Moreover the expressions of DNMT1, DNMT3a and DNMT3b were significantly positively correlated with the HPV positive（P〈0.05）. Conclusion The expression spectrum of DNMT has obvious changes in the cervical tissues,moreover HPV high-risk subtype infection is closely correlated with the increased expression of DNMT1 ,DNMT3a and DNMT3h.