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谷胱甘肽S-转移酶-pi 1(glutathione S-transferase pi 1,GSTP1)基因是多种癌症的抑制基因。目前已有多项研究探讨GSTP1基因启动子区甲基化检测在前列腺癌(prostate cancer,PCa)临床诊断中的意义,但尚无系统性评估。本研究通过检索Pub Med、Web of Science数据库,收集相关英文文献进行Meta分析,对GSTP1基因启动子区甲基化检测在PCa临床诊断中的意义做出系统性评估。最终有27篇文献,共计3 183例样本纳入本研究,包含2 067例PCa样本及1 116例对照样本。Meta分析结果,PCa患者GSTP1基因启动子区相比正常对照组呈现显著高甲基化,差异有统计学意义(OR=17.98,95%CI:12.16~26.58,p<0.000 1)。不同亚组(人种,样本类型及检测方法等)组间无显著性差异。上述研究的合并敏感度及特异度分别为0.70和0.96。此外,我们从TCGA(the cancer genome atlas,TCGA)数据库中选取425例前列腺腺癌(prostate adenocarcinoma,PRAD)组织与54例癌旁组织的高通量全基因组甲基化芯片数据进行验证分析后显示,GSTP1基因启动子区9个CpG位点中的7个位点,癌症组织相比癌旁组织呈现显著高甲基化水平。其敏感度均在0.85以上,特异度及AUC区间均在0.90以上,FDR<1×10~(-20)。综上,Meta分析和TCGA均显示PCa患者GSTP1基因启动子区相比正常对照组呈现显著高甲基化,且诊断特异度与敏感度均较高,是非常有前景的PCa诊断标志物,对PCa的临床诊断具有借鉴意义。
The glutathione S-transferase pi 1 (GSTP1) gene is a suppressor of many cancers. There are many studies to explore the significance of methylation detection of GSTP1 promoter in the clinical diagnosis of prostate cancer (PCa), but there is no systematic evaluation yet. In this study, PubMed and Web of Science databases were searched, and relevant English literature were collected for meta-analysis to systematically evaluate the significance of methylation detection of GSTP1 promoter in the clinical diagnosis of PCa. In the end, there were 27 articles and a total of 3,183 samples were included in the study, including 2,067 PCa samples and 1,116 control samples. Meta analysis showed that the promoter region of GSTP1 gene in PCa patients showed a significant hypermethylation compared with the normal control group (OR = 17.98, 95% CI: 12.16-26.58, p 0.0001). There was no significant difference between different subgroups (race, sample type and test method). The combined sensitivity and specificity of the above studies were 0.70 and 0.96, respectively. In addition, we selected 425 cases of prostate adenocarcinoma (PRAD) tissues and 54 cases of paracancerous tissues from high-throughput whole-genome methylated microarray data from TCGA (database of TCGA) for verification and analysis , And seven of nine CpG sites in the promoter region of GSTP1 gene. The cancer tissues showed a significant hypermethylation level compared with the adjacent non-cancerous tissues. The sensitivity was above 0.85, specificity and AUC range were above 0.90, FDR <1 × 10 ~ (-20). In summary, Meta analysis and TCGA showed that PCa patients with GSTP1 gene promoter region compared with the normal control group showed significant hypermethylation, and the diagnosis of specificity and sensitivity are high, is a very promising diagnostic marker of PCa, PCa Clinical diagnosis has reference value.