Osminin S V, Vetshev F P, Rudenko V V, Zaletaev D V, Khorobrykh T V, Nemtsova M V
Klin Lab Diagn. 2016 Oct;61(10):681-5.
The development of disease of Barrett's esophagus is based on processes of metaplasia of epithelium of esophagus when as a result of reflux of gastric juice and bile acids the normal planocellular epithelium of esophagus is replaced by cylindrical epithelium of intestinal type. Thereupon, Barrett's esophagus is progressing up to dysplasia and adenocarcinoma of esophagus. The progression from precancerous states up to tumor is related to development of genome disorders in cells associated with malignant transformation. The genetic and epigenetic alterations conditioning tumor growth can be used as markers of prognosis of clinical course of disease. To receive possible markers of progression of Barrett's esophagus the study was organized concerning methylation of such genes-suppressors of tumor growth as MGMT, CDH1, p16/CDKN2A, DAPK, RAR-β and RUNX3 in patients with Barrett's esophagus and adenocarcinoma of esophagus. The effectiveness of applied anti-reflux surgical treatment was evaluated too. The abnormal methylation of studied genetic panel in patients with Barrett's esophagus prior to surgical treatment was observed reliably more frequently in altered epithelium as compared with unaltered epithelium (p<0.0001), under dysplasia as compared with metaplasia (p<0.0358) and in the presence of long (>3 cm) segments of altered epithelium as compared with short (<3 cm) segments (p=0.0068). In normal epithelium, prior to operation, abnormal methylation of panel of genes was detected in 7/60 (12%) of patients. Against the background of surgical treatment number of long and short segments of altered epithelium of esophagus reliably decreased (p<0.05). At that, in short segments after operation rate of methylation increased significantly (p=0.0068). Though after operation number of patients with Barrett's esophagus and dysplasia and metaplasia decreased, the rate of abnormal methylation in the other patients increased. It is demonstrated that anti-reflux operation ameliorates condition of mucous membrane of esophagus under Barrett's esophagus. However, in cases without regression significant increasing of rate of abnormal methylation of studied panel of genes is occurred. This is a proof that abnormal methylation of system of genes is related to worse response to application of anti-reflux surgical treatment.
巴雷特食管疾病的发展基于食管上皮化生过程，即由于胃液和胆汁酸反流，食管正常的扁平上皮被肠型柱状上皮取代。随即，巴雷特食管会发展至食管发育异常和腺癌。从癌前状态发展到肿瘤与细胞中与恶性转化相关的基因组紊乱的发展有关。影响肿瘤生长的遗传和表观遗传改变可作为疾病临床进程预后的标志物。为了获得巴雷特食管进展的可能标志物，针对巴雷特食管和食管腺癌患者中肿瘤生长抑制基因MGMT、CDH1、p16/CDKN2A、DAPK、RAR-β和RUNX3的甲基化情况开展了研究。同时也评估了所应用的抗反流手术治疗的效果。与未改变的上皮相比，在手术治疗前，巴雷特食管患者中所研究基因面板的异常甲基化在改变的上皮中更频繁地被可靠观察到（p<0.0001），在发育异常时比化生时更频繁（p<0.0358），并且在存在长（>3 cm）段改变的上皮时比短（<3 cm）段更频繁（p=0.0068）。在术前正常上皮中，60例患者中有7例（12%）检测到基因面板的异常甲基化。在手术治疗的背景下，食管改变上皮的长段和短段数量可靠地减少（p<0.05）。此时，术后短段上皮中甲基化率显著增加（p=0.0068）。虽然术后巴雷特食管、发育异常和化生患者的数量减少，但其他患者的异常甲基化率增加。结果表明，抗反流手术改善了巴雷特食管下食管黏膜的状况。然而，在无消退的情况下，所研究基因面板的异常甲基化率显著增加。这证明基因系统的异常甲基化与抗反流手术治疗的较差反应有关。
