Tang Yuanyuan, Jiang Shusuan, Gu Yinmin, Li Weidong, Mo Zengnan, Huang Yuanjie, Li Tianyu, Hu Yanling
Guangxi Reproductive Medical Research Center, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Department of Urology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Oncotarget. 2017 Mar 22;8(35):58199-58209. doi: 10.18632/oncotarget.16437. eCollection 2017 Aug 29.
Prostate cancer (PCa) is the most common tumor in elderly men. However, the specificity and sensitivity of serum prostate-specific antigen levels in PCa diagnosis are controversial. This study aims to reveal a novel diagnosis biomarker in PCa.
The differential methylated CpG sites between 423 primary PCa and 39 adjacent samples from The Cancer Genome Atlas (TCGA) on Illumina HumanMethylation 450 platform were analyzed. The diagnostic methylation markers were mined using the Prediction Analysis of Microarrays package in Bioconductor. Then, the Gene Expression Omnibus data was used for verification. Pyrosequencing was applied to improve methylation levels of five CpGs (cg06363129, cg08843517, cg05385513, cg07220448 and cg11417025).
The area under curve of receiver operating characteristic of eight diagnostic methylation CpGs (cg06363129, cg08843517, cg03576469, cg05385513, cg07220448, cg11417025, cg20883831, and cg23824801) in TCGA data ranged from 0.910 to 0.939. Except for cg20883831 and cg23824801, the correlations between methylation levels of six other sites and their expressions in patients were significant (r > 0.5 and P < 0.001). The methylation level of cg06363129 was significantly different between the groups of Gleason Score (GS) = 7 and GS ≥ 8 (P < 0.05). Pyrosequencing in our samples confirmed that four diagnostic methylation sites (cg06363129, cg08843517, cg05385513, and cg11417025) had high diagnostic efficacy.
The combined diagnosis of four methylation CpGs sites (cg06363129, cg08843517, cg05385513, and cg11417025) in the gene promoter has high tissue specificity and diagnostic efficacy for PCa. Results revealed a novel potential biomarker for prostate cancer diagnosis.
前列腺癌（PCa）是老年男性中最常见的肿瘤。然而，血清前列腺特异性抗原水平在PCa诊断中的特异性和敏感性存在争议。本研究旨在揭示一种PCa的新型诊断生物标志物。
分析了来自癌症基因组图谱（TCGA）的423例原发性PCa和39例相邻样本在Illumina HumanMethylation 450平台上的差异甲基化CpG位点。使用生物导体中的微阵列预测分析软件包挖掘诊断甲基化标记。然后，利用基因表达综合数据库数据进行验证。采用焦磷酸测序法提高5个CpG位点（cg06363129、cg08843517、cg05385513、cg07220448和cg11417025）的甲基化水平。
TCGA数据中8个诊断性甲基化CpG位点（cg06363129、cg08843517、cg03576469、cg05385513、cg07220448、cg11417025、cg20883831和cg23824801）的受试者工作特征曲线下面积在0.910至0.939之间。除cg20883831和cg23824801外，其他6个位点的甲基化水平与患者中其表达之间的相关性显著（r>0.5且P<0.001）。Gleason评分（GS）=7组和GS≥8组之间cg06363129的甲基化水平存在显著差异（P<0.05）。我们样本中的焦磷酸测序证实4个诊断性甲基化位点（cg06363129、cg08843517、cg05385513和cg11417025）具有较高的诊断效能。
基因启动子中4个甲基化CpG位点（cg06363129、cg08843517、cg05385513和cg11417025）的联合诊断对PCa具有较高的组织特异性和诊断效能。结果揭示了一种用于前列腺癌诊断的新型潜在生物标志物。
