A risk prediction model of DNA methylation improves prognosis evaluation and indicates gene targets in prostate cancer

A risk prediction model of DNA methylation improves prognosis evaluation and indicates gene targets in prostate cancer
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DNA 甲基化的风险预测模型可改善预后评估并指示前列腺癌的基因靶点

DOI:
10.2217/epi-2019-0349
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发表时间:
2020-02-01
期刊:
影响因子:
3.8
通讯作者:
Song, Yongsheng
Song, Yongsheng
中科院分区:
医学4区
文献类型:
--
作者:
Zhang, Enchong;Hou, Xueying;Song, Yongsheng

文献摘要

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目的:前列腺癌(PCa)是世界范围内男性最常见的恶性肿瘤。虽然大多是无痛的,但PCa仍然对长期健康构成严重威胁。材料与方法:将癌症基因组图谱数据随机分为训练组和验证组。对训练组的DNA甲基化数据进行最小绝对收缩和选择算子回归来建立模型,并在验证组中进行验证。对RNA-seq数据进行加权相关网络分析以识别治疗靶点。对靶标进行功能验证(蛋白质印迹、定量实时PCR、细胞转染、Cell Counting Kit-8测定、集落形成测定、伤口愈合测定和transwell侵袭测定)。结果:该模型是一个独立的预测预后。FOXD 1的敲低抑制PCa的细胞增殖、迁移和侵袭。结论:该模型可用于评估患者的危险性,提示FOXD 1可能促进患者的不良预后。
Aim: Prostate cancer (PCa) is the most common malignancy found in males worldwide. Although it is mostly indolent, PCa still poses a serious threat to long-term health. Materials & methods: The Cancer Genome Atlas data were randomly divided into training and validation groups. Least absolute shrinkage and selection operator regression on DNA methylation data in the training group was conducted to build the model, which was validated in the validation group. Weighted correlation network analysis was conducted on RNA-seq data to identify the therapy target. Functional validation (western blot, quantitative real-time PCR, cell transfection, Cell Counting Kit-8 assay, colony formation assay, wound healing assay and transwell invasion assay) for the target was conducted. Results: The model is an independent predictor of prognosis. The knockdown of FOXD1 inhibits cell proliferation, migration and invasion of PCa. Conclusion: The risk of patients could be evaluated by the model, which revealed that FOXD1 might promote poor prognosis.