EMX1、miR-124a-3、NKX6-1甲基化与胃癌癌前疾病的关系

Correlation between EMX1,miR-124a-3,NKX6-1 methylation and gastric cancer precancerous diseases

目的探讨EMX1、miR-124a-3、NKX6-1基因甲基化与胃癌癌前疾病的关系。方法选取2015年6月—2020年2月于山东省临沂市人民医院内镜中心行胃镜及病理检查的192例患者作为研究对象。依据胃癌的发展模式(Correa级联),将其分为慢性非萎缩性胃炎组(95例)、慢性萎缩性胃炎组(86例)和胃癌组(11例);依据慢性胃炎不同萎缩程度(病理)分为低萎缩组(104例)、高萎缩组(77例);依据慢性萎缩性胃炎肠化程度分为低度肠化组(31例)、高度肠化组(55例);根据内镜下慢性萎缩性胃炎木村-竹本分类分为低度萎缩组(24例)、中度萎缩组(48例)、高度萎缩组(14例)组。比较各组EMX1、miR-124a-3、NKX6-1基因不同位点甲基化水平。结果慢性萎缩性胃炎组EMX1基因(72920455、72920466、72920469)与miR-124a-3基因(63178433、63178444、63178452)位点甲基化水平高于慢性非萎缩性胃炎组,差异均有统计学意义(均P<0.05)。胃癌组NKX6-1基因(84496988、84496933、84496882、84496840)位点甲基化水平低于慢性非萎缩性胃炎组及慢性萎缩性胃炎组;慢性萎缩性胃炎组NKX6-1基因(84496988、84496933、84496882、84496840)位点甲基化水平高于慢性非萎缩性胃炎组,差异均有统计学意义(均P<0.05)。高萎缩组EMX1基因(72920466、72920469、72920484),miR-124a-3基因(63178433、63178452、63178485)与NKX6-1基因(84497016、84496979、84496975)位点甲基化水平高于低萎缩组,差异均有统计学意义(均P<0.05)。高度肠化组EMX1基因(72920455、72920466、72920469),miR-124a-3基因(63178334、63178377、63178433)与NKX6-1基因(84497016、84496979、84496975)位点甲基化水平高于低度肠化组,差异均有统计学意义(均P<0.05)。高度萎缩组EMX1基因(72920581、72920627、72920639)位点甲基化水平高于低度萎缩组和中度萎缩组,差异均有统计学意义(均P<0.05)。高度萎缩组miR-124a-3基因(63178345、63178383、63178444)与NKX6-1基因(84496965、84496893、84496884)位点甲基化水平高于低度萎缩组,差异均有统计学意义(均P<0.05)。结论EMX1、miR-124a-3、NKX6-1基因甲基化可能在胃癌癌前疾病萎缩及肠化的发展过程中发挥重要作用。但其具体机制仍有待进一步深入探究。

Objective To investigate the correlation between EMX1,miR-124a-3,NKX6-1 methylation and gastric cancer precancerous diseases.Methods From June 2015 to February 2020,192 patients who underwent gastroscopy with pathological examination at Endoscopy Center of Linyi People’s Hospital of Shandong Province were selected as study objects.They were divided into chronic non-atrophic gastritis group(95 cases),chronic atrophic gastritis group(86 cases),and gastric cancer group(11 cases)according to the development model of gastric cancer(Correa cascade);according to different degrees of chronic gastritis atrophy(pathology),they were divided into low atrophy group(104 cases)and high atrophy group(77 cases);according to the degree of intestinal metaplasia of chronic atrophic gastritis,they were divided into low intestinal metaplasia group(31 cases)and high intestinal metaplasia group(55 cases);according to the Kimura-Takemoto classification of chronic atrophic gastritis under endoscopy,They were divided into low atrophy group(24 cases),moderate atrophy group(48 cases),and high atrophy group(14 cases).The methylation levels at different sites of EMX1,miR-124A-3 and NKX6-1 genes in each group were compared.Results The methylation levels of EMX1 gene(72920455,72920466 and 72920469)and miR-124a-3 gene(63178433,63178444 and 63178452)sites in chronic atrophic gastritis group were higher than those in chronic non-atrophic gastritis group,and the differences were all statistically significant(all P<0.05).The methylation levels of NKX6-1 gene(84496988,84496933,84496882,84496840)sites in gastric cancer group were lower than those in chronic non-atrophic gastritis group and chronic atrophic gastritis group;the methylation levels of NKX6-1 gene(84496988,84496933 and 84496882,84496840)sites in chronic atrophic gastritis group were higher than those in chronic non-atrophic gastritis group,and the differences were all statistically significant(all P<0.05).The methylation levels of EMX1 gene(72920466,72920469 and 72920484),miR-124a-3 gene(63178433,63178452 and 63178485)and NKX6-1 gene(84497016,84496979,84496975)sites in high atrophy group were higher than those in low atrophy group,and the differences were all statistically significant(all P<0.05).The methylation levels of EMX1 gene(72920455,72920466 and 72920469),miR-124a-3 gene(63178334,63178377 and 63178433)and NKX6-1 gene(84497016,84496979 and 84496975)sites in high intestinal metaplasia group were higher than those in low intestinal metaplasia group,and the differences were all statistically significant(all P<0.05).The methylation levels of EMX1 gene(72920581,72920627 and 72920639)sites in high atrophy group were higher than those in low atrophy group and moderate atrophy group,and the differences were all statistically significant(all P<0.05);the methylation levels of miR-124a-3 gene(63178345,63178383 and 63178444)and NKX6-1 gene(84496965,84496893 and 84496884)sites in high atrophy group were higher than those in low atrophy group,and the differences were all statistically significant(all P<0.05).Conclusion Methylation of EMX1,miR-124a-3 and NKX6-1 genes may play an important role in the development of precancerous atrophy and intestinal metaplasia of gastric cancer.However,its specific mechanism remains to be further explored.