Correlation between EMX1, miR-124a-3, NKX6-1 methylation and gastric cancer precancerous diseases
SUN Liangxu1,2 PENG Lijun2▲ GUO Anbing2 ZHANG Yanqing2 LU Lin2 JI Buxi2
1.Graduate Faculty, Shandong First Medical University Shandong Academy of Medical Sciences, Shandong Province, Ji’nan 250062, China;
2.Department of Gastroenterology, Linyi People’s Hospital, Shandong Province, Linyi 276000, China
Abstract：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.
[1] Bray F，Ferlay J，Soerjomataram I，et al. Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin，2018，68（6）：394-424.
[2] 王宁，刘硕，杨雷，等.2018全球癌症统计报告解读[J].肿瘤综合治疗电子杂志，2019，5（1）：87-97.
[3] 胃癌诊疗规范（2018年版）[J].肿瘤综合治疗电子杂志，2019，5（1）：55-82.
[4] 田玲蓉，艾耀伟，颜学良.早期胃癌筛查方法的研究进展[J].基层医学论坛，2019，23（28）：4132-4134.
[5] Tahara T，Arisawa T. DNA methylation as a molecular bio-marker in gastric cancer [J]. Epigenomics，2015，7（3）：475-486.
[6] Pirini F，Noazin S，Jahuira-Arias MH，et al. Early detection of gastric cancer using，globalgenome-wide and IRF4，ELMO1，CLIP4 and MSC DNA methylation in endoscopic biopsies [J]. Oncotarget，2017，8（24）：38501-38516.
[7] Kojima K，Minatani N，Ushiku H，et al. Prediction of onset of remnant gastric cancer by promoter DNA methylation of CDO1/HOPX/Reprimo/E-cadherin [J]. Oncotarget，2019， 10（25）：2423-2434.
[8] Ma X，Chen H，Wang G，et al. DNA methylation profiling to predict overall survival risk in gastric cancer：development and validation of a nomogram to optimize clinical management [J]. J Cancer，2020，11（15）：4352-4365.
[9] Asada K，Nakajima T，Shimazu T，et al. Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study [J]. Gut，2015，64（3）：388-396.
[10] Maeda M，Nakajima T，Oda I，et al. High impact of methylation accumulation on metachronous gastric cancer：5-year follow-up of a multicentre prospective cohort study [J]. Gut，2017，66（9）：1721-1723.
[11] 房静远，杜奕奇，刘文忠，等.中国慢性胃炎共识意见（2017年，上海）[J].胃肠病学，2017，22（11）：670-687.
[12] 中华医学会病理分会消化病理学组筹备组.慢性胃炎及上皮性肿瘤胃黏膜活检病理诊断共识[J].中华病理学杂志，2017，46（5）：289-293.
[13] Kimura K，Takemoto T. An Endoscopic Recognition of the Atrophic Border and its Significance in Chronic Gastritis [J]. Endoscopy，1969，1（3）：87-97.
[14] 杜迎新，邓靖宇，梁寒.DNA甲基化在胃癌中的研究进展[J].天津医科大学学报，2019，25（2）：189-193.
[15] Choi RS，Lai WYX，Lee LTC，et al. Current and future molecular diagnostics of gastric cancer [J]. Expert Rev Mol Diagn，2019，19（10）：863－874.
[16] Lian Q，Wang B，Fan L，et al. DNA methylation data-based molecular subtype classification and prediction in patients with gastric cancer [J]. Cancer Cell Int，2020， 20：349.
[17] Ebrahimi V，Soleimanian A，Ebrahimi T，et al. Epigenetic modifications in gastric cancer：Focus on DNA methylation [J]. Gene，2020，742：144577.
[18] Schneider BG，Mera R，Piazuelo MB，et al. DNA Methylation Predicts Progression of Human Gastric Lesions [J]. Cancer Epidemiol Biomarkers Prev，2015，24（10）：1607-1613.
[19] Li C，Zheng Y，Pu K，et al. A four-DNA methylation signature as a novel prognostic biomarker for survival of patients with gastric cancer [J]. Cancer Cell Int，2020， 20：88.
[20] Bai Y，Wei C，Zhong Y，et al. Development and Validation of a Prognostic Nomogram for Gastric Cancer Based on DNA Methylation-Driven Differentially Expressed Genes [J]. Int J Biol Sci，2020，16（7）：1153-1165.
[21] Maeda M，Yamashita S，Shimazu T，et al. Novel epigenetic markers for gastric cancer risk stratification in individuals after Helicobacter pylori eradication [J]. Gastric Cancer，2018，21（5）：745-755.
[22] Tahara S，Tahara T，Horiguchi N，et al. DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication [J]. Int J Cancer，2019， 144（1）：80-88.
[23] Chen X，Gole J，Gore A，et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test [J]. Nat Commun，2020，11（1）：3475.
[24] 邹天慧，廖晓宏，陈萦晅.慢性萎缩性胃炎癌变的预警、早期诊断与预防[J].临床荟萃，2019，34（5）：407-411.
[25] Chang S，Kuo C，Wu C，et al. NKX6.1 hypermethylation predicts the outcome of stage Ⅱ colorectal cancer patients undergoing chemotherapy [J]. Genes Chromosomes Cancer，2018，57（5）：268-277.
2021, Vol. 18 
京公网安备 11010502046598号