ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer
ZNF671 DNA methylation as a molecular predictor for the early recurrence of serous ovarian cancer
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ZNF671基因甲基化作为浆液性卵巢癌早期复发的分子预测指标
DOI：
10.1111/cas.13936
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发表时间：
2019-03-01
期刊：
影响因子：
5.7
通讯作者：
Kondo, Yutaka
中科院分区：
文献类型：
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作者：
Mase, Shoko;Shinjo, Keiko;Kondo, Yutaka
浆液性卵巢癌是最常见的上皮性卵巢癌。尽管使用手术和铂类化疗，许多患者在6个月内复发，称为铂类耐药。目前，缺乏预测浆液性卵巢癌早期复发的相关分子生物标志物与预后不良有关。为了确定早期复发的有效生物标志物，我们分析了治疗后早期复发的全基因组DNA甲基化状态特征。将癌症基因组图谱（TCGA）数据集中首次治疗后显示完全缓解的患者分为2组：早期复发浆液性卵巢癌（ERS，复发12个月，n = 158）。在两组之间鉴定的12个不同甲基化的探针中，我们发现ZNF 671是早期复发组中甲基化最显著的基因。78例浆液性卵巢癌的验证队列显示，ZNF 671 DNA甲基化的患者预后较差（P <0.05）。多变量分析显示，在TCGA数据集和我们的队列中，ZNF 671甲基化状态是预测浆液性卵巢癌患者复发的独立因素（分别为P = 0.049和P = 0.021）。功能分析显示，ZNF 671表达的缺失赋予卵巢癌细胞更多的迁移和侵袭表型。我们的数据表明ZNF 671在卵巢癌中具有抑癌作用，ZNF 671的DNA甲基化状态可能是浆液性卵巢癌铂类辅助化疗后复发的有效生物标志物。
Serous ovarian cancer is the most frequent type of epithelial ovarian cancer. Despite the use of surgery and platinum-based chemotherapy, many patients suffer from recurrence within 6 months, termed platinum resistance. Currently, the lack of relevant molecular biomarkers for the prediction of the early recurrence of serous ovarian cancers is linked to the poor prognosis. To identify an effective biomarker for early recurrence, we analyzed the genome-wide DNA methylation status characteristic of early recurrence after treatment. The patients in The Cancer Genome Atlas (TCGA) dataset who showed a complete response after the first therapy were categorized into 2 groups: early recurrence serous ovarian cancer (ERS, recurrence 12 months, n = 158). Among the 12 differently methylated probes identified between the 2 groups, we found that ZNF671 was the most significantly methylated gene in the early recurrence group. A validation cohort of 78 serous ovarian cancers showed that patients with ZNF671 DNA methylation had a worse prognosis (P < .05). The multivariate analysis revealed that the methylation status of ZNF671 was an independent factor for predicting the recurrence of serous ovarian cancer patients both in the TCGA dataset and our cohort (P = .049 and P = .021, respectively). Functional analysis revealed that the depletion of ZNF671 expression conferred a more migratory and invasive phenotype to the ovarian cancer cells. Our data indicate that ZNF671 functions as a tumor suppressor in ovarian cancer and that the DNA methylation status of ZNF671 might be an effective biomarker for the recurrence of serous ovarian cancer after platinum-based adjuvant chemotherapy.