GSTPl基因启动子甲基化与前列腺癌的相关性研究

Association between GSTPl gene promoter methylation and prostate cancer

背景与目的:谷胱甘S-转移酶P1(glutathione S-transferase P1,GSTP1)保护细胞避免DNA损伤和癌细胞形成,抑制GSTP1活性可以导致DNA损伤的敏感性增强和癌变发生的概率增加。该研究旨在研究前列腺癌组织中GSTPl基因甲基化与前列腺癌临床病理特征的关系。方法:收集2015年4月—2016年12月在海南省中医院和海口市人民医院住院的46例前列腺癌患者的前列腺癌组织及对应的包埋癌旁组织,应用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测GSTPl m RNA水平,通过甲基化特异性聚合酶链反应(methylation-specific polymerase chain reaction,MSP)检测GSTP1基因启动子区域Cp G岛的甲基化表达水平,然后与性别、年龄及肿瘤TNM分期等临床数据进行关联分析。结果:与癌旁组织比较,前列腺癌组织中GSTP1 m RNA表达水平降低(P<0.01),并且GSTP1 m RNA降低与GSTPl基因甲基化呈负相关(P<0.05);前列腺癌和癌旁组织中甲基化阳性率分别为66.0%和23.5%,差异有统计学意义(P<0.05);GSTP1基因的启动子甲基化频率与肿瘤分期显著相关(r=073,P<0.05),而与其他临床特征无明显相关性(P>0.05)。结论:GSTP1基因启动子甲基化可能造成GSTP1基因低表达,与前列腺癌发病明显相关,有望成为检测及诊断前列腺癌的新方法。

Background and purpose： Glutathione S-transferase P1 （GSTP1） protects cells from DNA damage and cancer cell formation. Inhibition of GSTP1 activity could increase susceptibility to DNA damage and increase the risk of cancer occurrence, which was associated with cancer. This study aimed investigate the relationship between GSTPl gene methylation and clinical pathological features of prostate cancer. Methods： Forty-six patients with prostate cancer who were hospitalized in Hainan Provincial Hospital of Traditional Chinese Medicine and Haikou People’s Hospital from Apr. 2015 to Dec. 2016 were enrolled in this study. The expression level of GSTPl mRNA was detected by real-time fluorescence quantitative polymerase chain reaction （RTFQ-PCR）. The methylation level of CpG island in GSTP1 gene promoter region was detected by methylation-specific polymerase chain reaction （MSP）, then its associations with the gender, age, tumor TNM staging and other clinical data were analyzed. Results： The expression of GSTP1 mRNA in prostate cancer tissues was lower than that in para-cancerous tissues （P〈0.01）, and the decrease of GSTP1 mRNA was negatively correlated with GSTPl methylation （P〈0.05）. The positive rates of methylation in prostate cancer and para-cancerous tissues were 66.0% and 23.5%, respectively, and the difference was statistically significant （P〈0.05）. The promoter methylation frequency of GSTP1 gene was significantly correlated with different tumor staging （r=073, P〈0.05）. However, compared with other clinical trials, there was no significant difference （P〉0.05）. Conclusion： GSTP1 gene promoter methylation may cause low expression of GSTP1 gene, which is closely related to the pathogenesis of prostate cancer. Monitoring GSTP1 gene promoter methylation is expected to be a new method for the detection and diagnosis of prostate cancer.