Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Arch Med Res. 2016 May;47(4):285-92. doi: 10.1016/j.arcmed.2016.07.011.
Methylation status of RUNX3 remains largely unknown in gastric cancer (GC). The aim of this study was to prognostically evaluate the methylation level of CpG sites within RUNX3 promoter region in GC.
Using pyrosequencing, we quantitatively explored the methylation status of 8 CpG sites within RUNX3 promoter region for 76 gastric cancer and 24 normal gastric tissues. We then analyzed the association between methylation level of each CpG site and clinicopathological characteristics and outcomes in the cohort.
Methylation of RUNX3 promoter was significantly higher in GC than normal subjects. Overall methylation level was closely associated with tumor invasion and TNM stage. Positive associations were found between hypermethylation of the following concerned sites and variables: site -1392, -1397, -1403, -1415 and tumor invasion, as well as TNM stage; site -1392 and lymph node metastasis along with number of lymph node metastases; site -1415 and cancer recurrence; site -1403, -1415 and cancer-related deaths. In multivariate analysis, tumor invasion was correlated with sites -1392 and -1397. Lymph node metastasis was associated with site -1392. Most importantly, methylation of site -1415 was associated with poor survival by using Cox survival regression.
Analysis of RUNX3 gene promoter by quantitative pyrosequencing suggested methylation status of RUNX3 is different in normal and tumor tissues. RUNX3 methylation level is associated with GC, especially the methylation at site -1415 contributes to the poor prognosis in GC. Thus, RUNX3 methylation may serve as a valuable diagnostic and prognostic biomarker in GC.
RUNX3 的甲基化状态在胃癌（GC）中仍然很大程度上未知。本研究的目的是预测性评估 RUNX3 启动子区域内 CpG 位点的甲基化水平在 GC 中的作用。
使用焦磷酸测序，我们定量探索了 RUNX3 启动子区域内 8 个 CpG 位点在 76 例胃癌和 24 例正常胃组织中的甲基化状态。然后，我们分析了每个 CpG 位点的甲基化水平与队列中临床病理特征和结局之间的关系。
GC 中 RUNX3 启动子的甲基化明显高于正常对照。总体甲基化水平与肿瘤浸润和 TNM 分期密切相关。以下关注的位点的高甲基化与变量之间存在正相关：-1392、-1397、-1403、-1415 位点与肿瘤浸润和 TNM 分期；-1392 位点与淋巴结转移和淋巴结转移数有关；-1415 位点与癌症复发有关；-1403、-1415 位点与癌症相关死亡有关。在多变量分析中，肿瘤浸润与 -1392 和 -1397 位点相关。淋巴结转移与 -1392 位点相关。最重要的是，Cox 生存回归分析表明 -1415 位点的甲基化与不良生存相关。
通过定量焦磷酸测序分析 RUNX3 基因启动子表明，RUNX3 的甲基化状态在正常和肿瘤组织中不同。RUNX3 甲基化水平与 GC 相关，特别是 -1415 位点的甲基化有助于 GC 的不良预后。因此，RUNX3 甲基化可能成为 GC 中一种有价值的诊断和预后生物标志物。
