Deng Jingyu, Liang Han, Ying Guoguang, Zhang Rupeng, Wang Baogui, Yu Jun, Fan Daiming, Hao Xishan
Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China.
Oncotarget. 2014 May 30;5(10):3173-83. doi: 10.18632/oncotarget.1888.
RNF 180, a novel tumor suppressor, has been implicated in the carcinogenesis and progress of gastric cancer. At present study, we found that lower expression of RNA180 was specific in gastric cancer tissues, and the inconsistently methylated levels of RNF180 promoter were identified in the gastric cancer tissues. Importantly, we demonstrated that the methylated CpG site count and four hypermethylated CpG sites (-116, -80, +97, and +102) were significantly associated with the survival of 400 gastric cancer patients, respectively. With multivariate survival analyses, we demonstrated that both the methylation of combined CpG (-116, -80, +97, and +102) sites and N stage were the independent indictor of prognosis of gastric cancer patients. Eventually, the methylation of combined CpG (-116, -80, +97, and +102) sites was identified to have smaller AIC value than N stage by mean of AIC calculation with the Cox proportional hazards model. These findings indicated that the quantitative detection of RNF180 promoter methylation had the intensive feasibility for evaluation the prognosis of gastric cancer patients in clinic.
RNF 180是一种新型肿瘤抑制因子,与胃癌的发生和进展有关。在本研究中,我们发现RNA180在胃癌组织中表达较低,且在胃癌组织中发现RNF180启动子甲基化水平不一致。重要的是,我们证明甲基化CpG位点计数和四个高甲基化CpG位点(-116、-80、+97和+102)分别与400例胃癌患者的生存显著相关。通过多因素生存分析,我们证明联合CpG(-116、-80、+97和+102)位点的甲基化和N分期均为胃癌患者预后的独立指标。最终,通过Cox比例风险模型进行AIC计算,发现联合CpG(-116、-80、+97和+102)位点的甲基化的AIC值比N分期小。这些发现表明,RNF180启动子甲基化的定量检测在临床上评估胃癌患者预后具有较强的可行性。