Clinical significance of DAPK promoter hypermethylation in lung cancer: a meta-analysis.

Death-associated protein kinase 1 (DAPK) is an important serine/threonine kinase involved in various cellular processes, including apoptosis, autophagy, and inflammation. DAPK expression and activity are deregulated in a variety of diseases including cancer. Methylation of the DAPK gene is common in many types of cancer and can lead to loss of DAPK expression. However, the association between DAPK promoter hypermethylation and the clinicopathological significance of lung cancer remains unclear. In this study, we searched the MEDLINE, PubMed, Web of Science, and Scopus databases, systematically investigated the studies of DAPK promoter hypermethylation in lung cancer and quantified the association between DAPK promoter hypermethylation and its clinicopathological significance by meta-analysis. We observed that the frequency of DAPK methylation was significantly higher in lung cancer than in non-malignant lung tissues (odds ratio 6.02, 95% confidence interval 3.17-11.42, P<0.00001). The pooled results also showed the presence of a prognostic impact of DAPK gene methylation in lung cancer patients (odds ratio 3.63, 95% confidence interval 1.09-12.06, P=0.04). In addition, we summarized these findings and discuss tumor suppressor function, clinicopathological significance, and potential drug targeting of DAPK in lung cancer.

Value of promoter methylation of RASSF1A, p16, and DAPK genes in induced sputum in diagnosing lung cancers / 中南大学学报(医学版)

Objective To determine the aberrant methylation status of RASSF1A,p16 and DAPK gene promoter region in induced sputum from lung cancer patients and the value of their combined detection in diagnosing lung cancers. Methods Methylation-specific PCR (MSP) was used to detect the promoter methylation status of RASSF1A,p16, and DAPK genes in induced sputum and pathological tissues from 82 patients with lung cancers and 25 patients with pulmonary benign lesion.We also analyzed the relation between methylation status and clinical pathological data.Results The positive rates of promoter methylation of RASSF1A,p16, and DAPK genes in pathological tissues from patients with lung cancers were 63.4%,59.8%, and 58.5%, respectively,and those in induced sputum were 54.9%,48.8%,and 51.2%, respectively. The promoter methylation of RASSF1A,p16, and DAPK genes were not detected in patients with pulmonary benign lesion.There was a significant difference between the lung cancer group and pulmonary benign lesion group (P＜0.05). The methylation rate of RASSF1A gene was significantly lower in the middle and high differentiation and non-metastastic lymph node of lung cancer tissues than that in the poor differentiation and the metastatic lymph node of lung cancer tissues(P＜0.05), and was not correlated with age, sex, smoking index, clinical stage, and pathological types.The methylation rate of p16, and DAPK genes was not significantly correlated with all the above mentioned factors (P＞0.05). The methylation rate of joint detecting RASSF1A, p16, and DAPK genes was 73.2%. Conclusion Joint detection for promoter hypermethylation of RASSF1A, p16, and DAPK genes in induced sputum may be used as a simple and effective index of the diagnosis and prognose of lung cancers, and can improve the positive rate.

Analysis of promoter hypermethylation of death-asscciated protein kinase gene in blood from non-small cell lung cancer patients / 医学研究生学报

Objective: To analyze the aberrant methylation of death-asscciated protein kinase (DAPK) gene in blood from non-small cell lung cancer (NSCLC) patients and to evaluate its clinical significance. Methods: A methylation-specific PCR was performed for the detection of promoter hypermethylation of DAPK gene in blood DNA from 65 cases of NSCLC patients,and the relation of the aberrant methylation of DAPK gene and the clinical pathological data was analyzed. Results: 30.8% (20/65) of the blood from 65 cases of NSCLC patients showed hypermethylation in DAPK promoter, whereas no methylated DAPK gene promoter was found in blood from normal control or patients with benign lung diseases. DAPK gene promoter methylation in blood did not strongly correlate with the pathological class, stage, metastasis and differentiation of NSCLC. Conclusion: Detection of the aberrant methylation of DAPK gene in blood DNA from NSCLC patients might offer an effective means for the earlier auxiliary diagnosis of the malignancy.