p16基因甲基化与胃黏膜异型增生恶性转化的关系

发布时间：2018-03-19 18:32

本文选题：胃癌　切入点：异型增生　出处：《中华肿瘤防治杂志》2017年07期 　论文类型：期刊论文

【摘要】：目的山东省临朐县是我国北方胃癌高发区之一,人群中胃黏膜异型增生(dysplasia,DYS)病变所占比例较高。DYS是胃黏膜癌前病变发展的高级阶段,具有显著的恶性转化潜能。本研究探讨p16基因甲基化与DYS病变恶性转化的关系,验证其作为胃癌预警标志物的应用价值。方法以胃癌高发现场长期胃镜随访队列为基础,对101例来自山东省临朐县胃癌高发区且随访至2015-12-31的DYS病例,采用Methylight方法定量检测胃黏膜组织p16基因甲基化水平,评价其与DYS进展为胃癌风险的关系。结果在进展为胃癌组,p16基因甲基化百分比中位数(四分位数)为1.30%(0.13%~1.87%),显著高于非进展组的0.67%(0~1.15%),P=0.047。与p16基因低甲基化者相比,高甲基化水平的DYS患者进展为胃癌的风险显著增加,OR=3.67,95%CI为1.31~10.34。进一步分析发现幽门螺杆菌(H.pylori)感染阳性者p16基因甲基化百分比中位数(0.98%)明显高于阴性者(0.01%),P0.001;分层分析发现,p16基因高甲基化同时H.pylori感染阳性者进展为胃癌的风险进一步增加,OR=5.14,95%CI为1.57~16.82。通过分析p16基因甲基化水平与DYS病例进展为胃癌的时间关系,发现随着胃癌诊断时间的临近,p16基因甲基化水平有缓慢升高的趋势,但差异未见统计学意义。结论胃黏膜组织p16基因甲基化水平升高可作为DYS患者发生恶性转化的潜在预警标志物。
[Abstract]:Objective Linqu County of Shandong Province is one of the high incidence areas of gastric cancer in northern China. The proportion of gastric mucosal dysplasia dysplasia DYSs is high. DYS is the advanced stage of gastric precancerous lesion development. This study was designed to investigate the relationship between p16 gene methylation and malignant transformation of DYS lesions, and to verify the value of p16 gene methylation as an early warning marker for gastric cancer. The methylation level of p16 gene in gastric mucosa tissue was quantitatively detected by Methylight in 101 cases of DYS from Linqu County, Shandong Province, who were followed up to 2015-12-31. Results the median methylation percentage (quartile number) of p16 gene methylation in advanced gastric cancer group was 1.30 ~ 0.13 and 1.87%, which was significantly higher than that in non-progressive group. The risk of progression to gastric cancer in DYS patients with high methylation level was significantly higher than that in patients with high methylation level. The CI of 3.67-95 CI was 1.31n 10.34. Further analysis showed that the median methylation percentage of p16 gene was 0.98% in patients with Helicobacter pylori infection and 0.98% higher than that in negative patients (P 0.001). Stratified analysis found that the percentage of p16 gene methylation was significantly higher in patients with H. pylori infection than in those with negative H.pylori infection (P 0.001). Hypermethylation of p16 gene and progression of H.pylori infection to gastric cancer further increased the risk of progression to gastric cancer in patients with DYS by analyzing the relationship between the methylation level of p16 gene and the progression of gastric cancer. It was found that the methylation level of p16 gene increased slowly as the diagnostic time of gastric cancer approached. Conclusion the elevated level of p16 gene methylation in gastric mucosa may be a potential marker for malignant transformation in patients with DYS.
【作者单位】：北京大学肿瘤医院暨北京市肿瘤防治研究所流行病学研究室和病因学研究室恶性肿瘤发病机制及转化研究教育部重点实验室;临朐县卫生局胃癌防治研究所;
【基金】：国家自然科学基金面上项目(81572774) 北京市科技计划(z151100001615022)
【分类号】：R735.2

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