RNF180是食管癌的潜在诊断和预后标志物  

RNF180 is a potential diagnostic and prognostic biomarker for esophageal cancer

作　　者：马梓粼 高嫒嫒 朱城 蔚晓远 张美英 苏小茉 刘迎娣 郭明洲 MA Zilin;GAO Aiai;ZHU Cheng;WEI Xiaoyuan;ZHANG Meiying;SU Xiaomo;LIU Yingdi;GUO Mingzhou(Department of Gastroenterology,the First Medical Center of Chinese PLA General Hospital,Beijing 100853;Medical College of Nankai University,China)

机构地区：[1]中国人民解放军总医院第一医学中心消化内科医学部,北京100853 [2]南开大学医学院

出　　处：《胃肠病学和肝病学杂志》2025年第3期313-317,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金委员会资助项目(81672138,82272632,82403742);国家重点研发计划(2018YFA0208902,2020YFC2002705);解放军总医院青年自主创新科学基金项目(22QNCZ027);北京市自然科学基金重点项目(7254313,7171008)。

摘　　要：目的探讨RNF180基因甲基化在食管癌患者中作为诊断与预后标志物的可能性。方法应用甲基化特异性PCR、TCGA数据库及633例食管癌患者组织对RNF180基因启动子区的甲基化状态进行分析。最后通过χ2检验、Kaplan-Meier生存分析和Cox回归分析,深入探讨RNF180甲基化与临床病理因素之间的关系。结果通过TCGA数据库分析发现RNF180转录起始位点上下游CpG位点的甲基化密度与mRNA的表达水平呈负相关(P<0.01)。应用甲基化特异性PCR检测,发现66.51%(421/633)的食管癌组织中发生甲基化,甲基化与肿瘤分期、分化程度、淋巴结及脉管癌栓或远处转移具有显著相关性(P<0.001)。RNF180甲基化患者的总生存期明显较非甲基化患者的总生存期短,是食管癌不良预后的独立危险因素(P<0.001)。结论TCGA数据分析提示RNF180在食管癌中的表达受启动子区甲基化的调控。RNF180在食管癌组织中的甲基化率为66.51%,与肿瘤的恶性程度、转移和生存期缩短相关,是食管癌潜在的诊断和预后标志物。Objective To investigate the potential of RNF180 gene methylation as a diagnostic and prognostic biomarker in esophageal cancer patients.Methods Methylation-specific PCR,TCGA database,and tissues from 633 esophageal cancer patients were employed to comprehensively analyze the methylation status of the RNF180 gene promoter region.Statistical analyses,includingχ2 tests,Kaplan-Meier survival analysis,and Cox regression analysis,were conducted to evaluate the correlations between RNF180 methylation and clinicopathological features.Results Analysis of the TCGA database demonstrated that methylation density of CpG sites upstream and downstream of the RNF180 transcription start site was significantly negatively correlated with RNF180 mRNA expression levels(P<0.01).Methylation-specific PCR detection revealed that 66.51%(421/633)of esophageal cancer samples exhibited RNF180 promoter methylation.Furthermore,methylation status was significantly correlated with tumor stage,differentiation degree,lymph node involvement,and the presence of vascular cancer emboli or distant metastasis(all P<0.001).Notably,Kaplan-Meier survival analysis indicated that patients with RNF180 methylation had significantly shorter overall survival compared to those without methylation,identifying RNF180 methylation as an independent risk factor for poor prognosis in esophageal cancer(P<0.001).Conclusion Analysis of TCGA data indicates that RNF180 expression in esophageal cancer is epigenetically regulated by promoter region methylation.With a methylation frequency of 66.51%(421/633)in esophageal cancer tissues,RNF180 methylation is significantly associated with tumor malignancy,metastasis,and reduced survival,identifying it as a promising candidate for both diagnostic and prognostic biomarkers in esophageal cancer.

关 键 词：RNF180 食管癌 DNA甲基化 甲基化特异性PCR 

分 类 号：R735.1[医药卫生—肿瘤]