Cathay General Hospital, Taipei, Taiwan.
Eur J Clin Invest. 2010 Apr;40(4):310-8. doi: 10.1111/j.1365-2362.2010.02266.x.
Specific tumour suppressor genes with promoter methylation in ovarian clear cell adenocarcinoma (OCCA) can be one important epigenetic mark distinguishing OCCA from ovarian serous adenocarcinoma (OSA), benign endometriotic cysts and normal ovarian epitheliums.
Five OCCA cell lines, 63 cancer tissues (48 OCCA and 15 OSA), 10 benign endometriotic cysts and five normal ovarian epitheliums were analysed by methylation-specific PCR using pooled DNAs to determine the methylation status of the promoter of the target genes, including genes for secreted frizzled-related proteins (sFRP1 to 5), adenomatous polyposis coli (APC), retinoblastoma protein 1 (Rb1), breast cancer 1 gene (BRCA1), p14(ARF), p15(INK4b), p16(INK4a) and survivin. Methylation frequencies of identified targets were further analysed with individual DNA samples.
The sFRP5 promoter was significantly methylated in all OCCA cell lines, with 64.6% in OCCA tissues compared with 13.3% in OSA, and 0% in benign endometriotic cysts and normal ovarian epitheliums (P < 0.0001). With a median follow-up of 44 months, the expected 5-year overall survival (OS) for patients with methylated sFRP5 promoter were significantly worse than for those with unmethylated sFRP5 (52% vs. 88%, P = 0.03). After adjusting for age, stage, and residual disease after primary surgery, patients with unmethylated sFRP5 promoter had an independent good prognostic factor in OS (P = 0.017).
The high percentage of promoter methylation in the sFRP5 gene in OCCA indicates its importance in the development of OCCA and is a potential useful marker for prognoses and target for treatment of OCCA.
在卵巢透明细胞腺癌（OCCA）中，具有启动子甲基化的特定肿瘤抑制基因可能是区分 OCCA 与卵巢浆液性腺癌（OSA）、良性子宫内膜异位囊肿和正常卵巢上皮的一个重要表观遗传标记。
使用混合 DNA 通过甲基化特异性 PCR 分析 5 种 OCCA 细胞系、63 份癌症组织（48 份 OCCA 和 15 份 OSA）、10 份良性子宫内膜异位囊肿和 5 份正常卵巢上皮，以确定目标基因启动子的甲基化状态，包括分泌卷曲相关蛋白（sFRP1 至 5）、腺瘤性结肠息肉病基因（APC）、视网膜母细胞瘤蛋白 1（Rb1）、乳腺癌 1 基因（BRCA1）、p14（ARF）、p15（INK4b）、p16（INK4a）和存活素。进一步用个体 DNA 样本分析鉴定靶点的甲基化频率。
sFRP5 启动子在所有 OCCA 细胞系中均显著甲基化，在 OCCA 组织中为 64.6%，而在 OSA 中为 13.3%，在良性子宫内膜异位囊肿和正常卵巢上皮中为 0%（P<0.0001）。中位随访 44 个月后，甲基化 sFRP5 启动子患者的预期 5 年总生存率（OS）明显差于未甲基化 sFRP5 患者（52%比 88%，P=0.03）。在校正年龄、分期和初次手术后残留疾病后，未甲基化 sFRP5 启动子患者的 OS 具有独立的良好预后因素（P=0.017）。
OCCA 中 sFRP5 基因启动子的高甲基化率表明其在 OCCA 发生发展中的重要性，是预测 OCCA 预后和治疗靶点的潜在有用标志物。
