摘要： 目的 探讨ZNF568基因表达和DNA甲基化与食管癌预后的关联。方法 采用R软件中的edgeR包、limma包对食管癌癌组织与癌旁组织ZNF568基因表达、DNA甲基化进行差异分析。使用Spearman秩相关分析ZNF568基因表达水平与DNA甲基化的关联。通过癌细胞系百科全书（CCLE）数据库中的食管癌数据，验证ZNF568基因表达水平与DNA甲基化的关联。使用Cox比例风险回归模型分析ZNF568基因表达联合DNA甲基化与食管癌患者预后的关联，进而构建预后生存风险的列线图模型。结果 ZNF568基因在癌组织中的甲基化程度高于癌旁组织（FDR<0.001），而ZNF568基因在癌旁组织中的表达水平高于癌组织（FDR< 0.001）；ZNF568基因表达水平与DNA甲基化存在负相关（P < 0.001）；在CCLE数据库中也发现ZNF568基因表达水平与DNA甲基化存在关联（P=0.002）。多因素Cox回归分析发现，ZNF568基因高表达、DNA低甲基化能改善食管癌预后（HR=0.70，95%CI：0.51~0.96，P=0.043）；ZNF568基因表达与DNA甲基化联合分析能很好地预测食管癌的预后，C指数为0.697。结论 ZNF568基因高表达、DNA低甲基化与食管癌预后相关，检测食管癌ZNF568基因表达水平与DNA甲基化有助于判断食管癌的预后。

ZNF568基因表达联合DNA甲基化分析与食管癌预后的关联

刘双¹, 林征¹, 俞凯莉¹, 陈辉林², 饶雯清¹, 胡志坚¹

1. 福建医科大学公共卫生学院流行病与卫生统计学系, 福州 350122;
2. 泉州市安溪县医院放疗科, 福建 泉州 352400

收稿日期:2020-12-04出版日期:2021-10-30发布日期:2021-10-11
通讯作者:胡志坚E-mail:hzj99955888@126.com
作者简介:刘双(1994-),男,博士研究生.
基金资助:国家重点研发计划精准医学研究重点专项2017年度项目（2017YFC0907100）；2018年福建省医学创新课题（2018-CX-38）；福建医科大学启航基金（2018QH2012）


关键词: 食管癌, ZNF568基因, 甲基化, 基因表达, 预后
Abstract: Objective To investigate the role of ZNF568 gene expression and DNA methylation in the prognosis of esophageal cancer. Methods The edgeR and limma packages were used to analyze the difference in ZNF568 gene expression and DNA methylation between esophageal cancerous and paracancerous tissues. Spearman rank correlation and multivariate Cox regression analysis was performed to determine the association between ZNF568 gene expression level and DNA methylation, after which a prognostic nomogram was established. Results The ZNF568 gene was more methylated in cancerous tissues than in paracancerous tissues (false discovery rate, FDR, < 0.001) but was more expressed in paracancerous tissues than in cancerous tissues (FDR < 0.001). ZNF568 gene expression level was negatively correlated with DNA methylation (P < 0.001). ZNF568 gene expression level was also associated with DNA methylation in the Cancer Cell Line Encyclopedia database (P=0.002). Multivariate Cox regression analysis showed that ZNF568 high expression level and DNA hypomethylation were associated with improved prognosis in patients with esophageal cancer (hazard ratio, 0.70; 95% confidence interval, 0.51-0.96; P=0.043). The combination of ZNF568 gene expression and DNA methylation can predict the prognosis of esophageal cancer with a C-index of 0.697. Conclusion ZNF568 high expression level and DNA hypomethylation were associated with the improved prognosis of esophageal cancer. Further detection of ZNF568 gene expression and DNA methylation could provide a novel biomarker for determining the prognosis of esophageal cancer.
Key words: esophageal cancer, ZNF568 gene, methylation, gene expression, prognosis
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