DLEC1 和 PBX3 启动子甲基化与外周血白细胞中胃癌风险和预后的关系。

Relationship between DLEC1 and PBX3 promoter methylation and the risk and prognosis of gastric cancer in peripheral blood leukocytes.

机构信息

Department of Epidemiology, College of Public Health, Harbin Medical University, 197 Xuefu Road, Harbin, 150081, Heilongjiang, People's Republic of China.

Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150081, Heilongjiang, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2020 May;146(5):1115-1124. doi: 10.1007/s00432-020-03171-4. Epub 2020 Mar 6.

DOI:10.1007/s00432-020-03171-4

PMID:32144534

Abstract

PURPOSE

Aberrant DNA methylation could regulate the expression of tumor suppressor gene DLEC1 and oncogene PBX3 and was related to the occurrence and prognosis of gastric cancer (GC). In this study, the associations between DLEC1 and PBX3 promoter methylation in peripheral blood leukocytes (PBLs) and the risk and prognosis of GC were investigated.

METHODS

The methylation status of DLEC1 and PBX3 promoter in PBLs of 368 GC cases and 382 controls was detected by the methylation-sensitive high-resolution melting (MS-HRM) method. Logistic and Cox regression were adopted to analyze the associations of DLEC1 and PBX3 methylation with GC risk and prognosis, respectively. Confounding biases were controlled by propensity score (PS).

RESULTS

Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220-3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. In the elderly group (≥ 60 years), DLEC1 Pm was associated with increased GC risk (OR 2.951, 95% CI 1.426-6.104, P = 0.004). The combined effects between DLEC1 methylation and consumption of dairy products, fried food intake and Helicobacter pylori (H. pylori) infection on GC risk were discovered (OR 3.461, 95% CI 1.847-6.486, P < 0.001, OR 3.246, 95% CI 1.708-6.170, P < 0.001 and OR 2.964, 95% CI 1.690-5.197, P < 0.001, respectively). Furthermore, DLEC1 and PBX3 methylation were not associated with GC prognosis.

CONCLUSION

DLEC1 methylation in PBLs and the combined effects of gene-environment can influence GC risk.

摘要

目的

异常的 DNA 甲基化可能调节肿瘤抑制基因 DLEC1 和癌基因 PBX3 的表达，与胃癌（GC）的发生和预后有关。本研究旨在探讨外周血白细胞（PBL）中 DLEC1 和 PBX3 启动子甲基化与 GC 风险和预后的关系。

方法

采用甲基敏感高分辨率熔解（MS-HRM）法检测 368 例 GC 病例和 382 例对照者 PBL 中 DLEC1 和 PBX3 启动子的甲基化状态。采用 logistic 和 Cox 回归分析 DLEC1 和 PBX3 甲基化与 GC 风险和预后的关系，采用倾向评分（PS）控制混杂偏倚。

结果

与阴性甲基化（Nm）相比，PS 中 DLEC1 阳性甲基化（Pm）与 GC 风险增加相关（OR 2.083，95%CI 1.220-3.558，P=0.007），但 PBX3 Pm 与 GC 风险无关。在老年组（≥60 岁）中，DLEC1 Pm 与 GC 风险增加相关（OR 2.951，95%CI 1.426-6.104，P=0.004）。发现 DLEC1 甲基化与乳制品摄入、油炸食品摄入和幽门螺杆菌（H. pylori）感染之间的联合作用对 GC 风险有影响（OR 3.461，95%CI 1.847-6.486，P<0.001，OR 3.246，95%CI 1.708-6.170，P<0.001 和 OR 2.964，95%CI 1.690-5.197，P<0.001）。此外，DLEC1 和 PBX3 甲基化与 GC 预后无关。