Zhang Yang, Chen Duo, Zhang Lian, Ma Jun-Ling, Zhou Tong, Li Zhe-Xuan, Liu Wei-Dong, You Wei-Cheng, Pan Kai-Feng
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
Linqu Public Health Bureau, Linqu, Shandong, 262600, People's Republic of China.
J Cancer. 2021 Oct 28;12(24):7326-7333. doi: 10.7150/jca.64613. eCollection 2021.
Methylation alterations may be involved in -associated gastric carcinogenesis. This study aims to explore the potential associated methylation biomarkers in blood leukocyte and gastric mucosa. Five candidate -associated aberrant methylation genes were selected from the previous genome-wide profiling panels and validated in blood leukocyte and gastric mucosa in multi-stages (case-control validation between positive and negative subjects and self-control validation before and after anti- treatment). methylation level was decreased in blood leukocyte (62.07% 46.33%, <0.001) and gastric mucosa (56.30% 32.42%, <0.001) of positive subjects compared to negative controls. While, methylation level was increased significantly in blood leukocyte (29.57% 56.02%, <0.001) and gastric mucosa (31.10% 47.50%, <0.001) of positive subjects compared to controls. After successful eradication, the methylation levels were increased from 44.87% to 60.88% (<0.001) for and decreased from 46.19% to 34.56% (<0.001) for in blood leukocyte. Similar increasing and decreasing methylation alterations were also found for the two genes after successful eradication in paired gastric mucosa. In TCGA database, an inverse relationship was found between methylation and mRNA expression (=-0.12, =0.027). The GC cases with higher expression levels showed significantly worse survival (HR, 2.09, 95%CI, 1.22-3.57, =0.007) compared to lower expression subjects. and methylation levels may be affected by infection in gastric mucosa and blood leukocyte. may be involved in advanced stage of GC development, although the possible mechanism still needs further study in precancerous lesions.
甲基化改变可能与胃癌发生相关。本研究旨在探索血液白细胞和胃黏膜中潜在的相关甲基化生物标志物。从先前的全基因组分析面板中选择了5个与胃癌相关的异常甲基化基因,并在血液白细胞和胃黏膜中进行多阶段验证(在阳性和阴性受试者之间进行病例对照验证以及在抗治疗前后进行自身对照验证)。与阴性对照相比,阳性受试者血液白细胞中的甲基化水平降低(62.07%对46.33%,P<0.001),胃黏膜中的甲基化水平也降低(56.30%对32.42%,P<0.001)。然而,与对照相比,阳性受试者血液白细胞中的甲基化水平显著升高(29.57%对56.02%,P<0.001),胃黏膜中的甲基化水平也显著升高(31.10%对47.50%,P<0.001)。成功根除幽门螺杆菌后,血液白细胞中该基因的甲基化水平从44.87%升至60.88%(P<0.001),而另一个基因的甲基化水平从46.19%降至34.56%(P<0.001)。在配对的胃黏膜中成功根除幽门螺杆菌后,这两个基因也发现了类似的甲基化增减变化。在TCGA数据库中,发现该基因甲基化与mRNA表达呈负相关(r=-0.12,P=0.027)。与低表达受试者相比,高表达水平的胃癌病例显示出显著更差的生存率(HR,2.09,95%CI,1.22-3.57,P=0.007)。幽门螺杆菌感染可能会影响胃黏膜和血液白细胞中的甲基化水平。幽门螺杆菌可能参与胃癌发展的晚期阶段,尽管其可能机制仍需要在癌前病变中进一步研究。