Jia Wenzhuo, Yu Tao, Cao Xianglong, An Qi, Yang Hua
Department of General Surgery, Beijing Hospital, National Center of Gerontology, China.
Medicine (Baltimore). 2016 Oct;95(43):e5040. doi: 10.1097/MD.0000000000005040.
The loss of death-associated protein kinase (DAPK) gene expression through promoter methylation is involved in many tumors. However, the relationship between DAPK promoter methylation and clinicopathological features of gastric cancer (GC) remains to be done. Therefore, we performed a meta-analysis to assess the role of DAPK promoter methylation in GC.
Literature databases were searched to retrieve eligible studies. The pooled odds ratios (ORs) with its 95% confidence intervals (CIs) were calculated using the Stata 12.0 software.
Final 22 available studies with 1606 GC patients and 1508 nonmalignant controls were analyzed. A significant correlation was found between DAPK promoter methylation and GC (OR = 3.23, 95% CI = 1.70-6.14, P < 0.001), but we did not find any significant association in Caucasian population, and in blood samples in subgroup analyses. DAPK promoter methylation was associated with tumor stage and lymph node status (OR = 0.69, 95% CI = 0.49-0.96, P = 0.03; OR = 1.50, 95% CI = 1.12-2.01, P = 0.007; respectively). However, we did not find that DAPK promoter methylation was associated with gender status and tumor histology.
Our findings suggested that DAPK promoter methylation may play a key role in the carcinogenesis and progression of GC. In addition, methylated DAPK was a susceptible gene for Asian population. However, more studies with larger subjects should be done to further evaluate the effect of DAPK promoter methylation in GC patients, especially in blood and Caucasian population subgroup.
死亡相关蛋白激酶（DAPK）基因通过启动子甲基化导致表达缺失与多种肿瘤相关。然而，DAPK启动子甲基化与胃癌（GC）临床病理特征之间的关系仍有待研究。因此，我们进行了一项荟萃分析以评估DAPK启动子甲基化在GC中的作用。
检索文献数据库以获取符合条件的研究。使用Stata 12.0软件计算合并比值比（OR）及其95%置信区间（CI）。
最终分析了22项可用研究，共纳入1606例GC患者和1508例非恶性对照。发现DAPK启动子甲基化与GC之间存在显著相关性（OR = 3.23，95%CI = 1.70 - 6.14，P < 0.001），但在白种人群以及亚组分析中的血液样本中未发现任何显著关联。DAPK启动子甲基化与肿瘤分期和淋巴结状态相关（OR分别为0.69，95%CI = 0.49 - 0.96，P = 0.03；OR为1.50，95%CI = 1.12 - 2.01，P = 0.007）。然而，未发现DAPK启动子甲基化与性别状态和肿瘤组织学相关。
我们的研究结果表明，DAPK启动子甲基化可能在GC的发生和发展中起关键作用。此外，甲基化的DAPK是亚洲人群的一个易感基因。然而，需要进行更多纳入更大样本量受试者的研究，以进一步评估DAPK启动子甲基化对GC患者的影响，特别是在血液样本和白种人群亚组中。
