死亡相关蛋白激酶启动子甲基化与非小细胞肺癌患者的临床病理及预后特征的相关性：一项队列研究

Death-associated protein kinase promoter methylation correlates with clinicopathological and prognostic features in nonsmall cell lung cancer patients: A cohort study.

作者信息

Yang Xiao-Yu, Zhang Jun, Yu Xiao-Ling, Zheng Guo-Feng, Zhao Fei, Jia Xiao-Jing

机构信息

Department of Pathology, Xinxiang Medical University, Xinxiang 453003, P.R, China.

Department of Radiation Therapy, The Second Hospital of Jilin University, Changchun 130000, Jilin, P.R. China.

出版信息

J Cancer Res Ther. 2018;14(Supplement):S65-S71. doi: 10.4103/0973-1482.158197.

DOI:10.4103/0973-1482.158197

PMID:29578152

Abstract

OBJECTIVE

The objective was to study the correlation between death-associated protein kinase (DAPK) promoter methylation and the clinicopathological and prognostic features in nonsmall cell lung cancer (NSCLC) patients.

MATERIALS AND METHODS

A total of 117 NSCLC patients were recruited into our study between December 2012 and December 2014. Methylation-specific polymerase chain reaction was employed to detect the methylation status of DAPK in cancer tissues, peficancerous tissues, and serum samples of 117 NSCLC patients. In addition, serum samples of 115 healthy subjects were analyzed as controls. A literature search of English and Chinese databases, based on predefined criteria, identified published studies closely related to this study. Data were extracted, and meta-analysis was performed using STATA 12.0 software (STATA Corporation, College Station, TX, USA).

RESULTS

Our study results showed that DAPK promoter methylation frequency was significantly higher in NSCLC tissues compared to peficancerous normal tissues (58.1% vs. 12.8%, χ = 52.45, P < 0.001). When serum samples were compared, DAPK methylation frequency in NSCLC patients was higher than the control group (27.4% vs. 0, χ = 37.07, P < 0.001). Our meta-analysis results demonstrated that DAPK methylation frequency was lower in tumor node metastasis (TNM) stage I-II compared to TNM stage III-IV (relative risk [RR] =0.87, 95% confidence interval [CI] =0.76-0.99, P = 0.041). DAPK promoter methylation frequency in NSCLC patients with lymph node metastasis was significantly higher compared to the patients with no metastases (RR = 1.26, 95% CI = 1.04-1.52, P = 0.020). Finally, the 5-year survival rate was lower in NSCLC patient group with high frequency of DAPK methylation, compared to the patient group with unmethylated DAPK (RR = 0.71, 95% CI = 0.56-0.89, P = 0.004).

CONCLUSION

Our results showed that DAPK promoter methylation is tightly correlated with clinicopathological features of NSCLC and is associated with poor prognosis in patients.

摘要

目的

研究死亡相关蛋白激酶（DAPK）启动子甲基化与非小细胞肺癌（NSCLC）患者临床病理特征及预后的相关性。

材料与方法

2012年12月至2014年12月期间，共有117例NSCLC患者纳入本研究。采用甲基化特异性聚合酶链反应检测117例NSCLC患者癌组织、癌旁组织及血清样本中DAPK的甲基化状态。此外，分析115例健康受试者的血清样本作为对照。根据预定义标准检索英文和中文数据库，确定与本研究密切相关的已发表研究。提取数据，并使用STATA 12.0软件（美国德克萨斯州大学站市STATA公司）进行荟萃分析。

结果

我们的研究结果显示，与癌旁正常组织相比，NSCLC组织中DAPK启动子甲基化频率显著更高（58.1%对12.8%，χ = 52.45，P < 0.001）。比较血清样本时，NSCLC患者中DAPK甲基化频率高于对照组（27.4%对0，χ = 37.07，P < 0.001）。我们的荟萃分析结果表明，与TNM III-IV期相比，肿瘤淋巴结转移（TNM）I-II期的DAPK甲基化频率较低（相对风险[RR]=0.87，95%置信区间[CI]=0.76-0.99，P = 0.041）。有淋巴结转移的NSCLC患者中DAPK启动子甲基化频率显著高于无转移患者（RR = 1.26，95% CI = 1.04-1.52，P = 0.020）。最后，与DAPK未甲基化的患者组相比，DAPK甲基化频率高的NSCLC患者组5年生存率较低（RR = 0.71，95% CI = 0.56-0.89，P = 0.004）。