Department of Thoracic Surgery, 26447Peking University First Hospital, Beijing, China.
Department of Pathology, 571674Shantou University Medical College, Shantou, Guangdong, China.
Int J Biol Markers. 2022 Mar;37(1):47-57. doi: 10.1177/17246008211067552. Epub 2021 Dec 22.
Death-associated protein kinase (DAPK) has a strong function of tumor suppression involving apoptosis regulation, autophagy, and metastasis inhibition. Hypermethylation of CpG islands in DAPK gene promoter region is one of the important ways to inactivate this tumor suppressor gene, which might promote lung carcinogenesis. However, the clinicopathological significance of the DAPK promoter hypermethylation in lung cancer remains unclear. In this study, we performed a meta-analysis trying to estimate the clinicopathological significance of DAPK promoter hypermethylation in non-small cell lung cancer (NSCLC).
A detailed literature search for publications relevant to DAPK gene promoter methylation and NSCLC was made in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, CSTJ, Wanfang databases, and SinoMed (CBM). The random-effects model and fixed-effects model were utilized to pool the relative ratio based on the heterogeneity test in the meta-analysis.
A total of 41 studies with 3348 patients were included. The frequency of DAPK methylation was significantly higher in NSCLC than in non-malignant control (odds ratio (OR) = 6.88, 95% confidence interval (CI): 4.17-11.35, < 0.00001). The pooled results also showed that DAPK gene promoter hypermethylation was significantly associated with poor prognosis for overall survival in patients with NSCLC (hazard ratio: 1.23, 95% CI:1.01-1.52, = 0.04). Moreover, DAPK gene promoter hypermethylation was significantly associated with squamous cell carcinoma (OR: 1.25, 95% CI: 1.01-1.54, = 0.04) and smoking behavior (OR: 1.42, 95% CI: 1.04-1.93, = 0.03) but not with TNM stage, tumor differentiation, age, or gender.
DAPK promoter hypermethylation might be a candidate diagnostic and prognostic tumor marker for NSCLC.
死亡相关蛋白激酶（DAPK）具有强大的肿瘤抑制功能，涉及凋亡调节、自噬和转移抑制。DAPK 基因启动子区域 CpG 岛的高甲基化是使这种肿瘤抑制基因失活的重要途径之一，这可能促进肺癌的发生。然而，DAPK 启动子在肺癌中的高甲基化的临床病理意义尚不清楚。在这项研究中，我们进行了一项荟萃分析，试图评估 DAPK 启动子高甲基化在非小细胞肺癌（NSCLC）中的临床病理意义。
在 PubMed、Embase、Cochrane 图书馆、Web of Science、中国国家知识基础设施、CSTJ、万方数据库和 SinoMed（CBM）中对与 DAPK 基因启动子甲基化和 NSCLC 相关的文献进行详细的文献检索。在荟萃分析中根据异质性检验，采用随机效应模型和固定效应模型来合并相对比值。
共纳入 41 项研究，共 3348 例患者。与非恶性对照相比，NSCLC 中 DAPK 甲基化的频率明显更高（比值比（OR）=6.88，95%置信区间（CI）：4.17-11.35， < 0.00001）。合并结果还表明，DAPK 基因启动子高甲基化与 NSCLC 患者总生存期的不良预后显著相关（风险比：1.23，95% CI：1.01-1.52， = 0.04）。此外，DAPK 基因启动子高甲基化与鳞状细胞癌（OR：1.25，95% CI：1.01-1.54， = 0.04）和吸烟行为（OR：1.42，95% CI：1.04-1.93， = 0.03）显著相关，但与 TNM 分期、肿瘤分化程度、年龄或性别无关。
DAPK 启动子高甲基化可能是 NSCLC 的一个有前途的诊断和预后肿瘤标志物。
