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

Li Y, Zhu M, Zhang X, Cheng D, Ma X - Drug Des Devel Ther (2015)

Bottom Line: Death-associated protein kinase 1 (DAPK) is an important serine/threonine kinase involved in various cellular processes, including apoptosis, autophagy, and inflammation.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou, People's Republic of China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The included studies investigated DAPK methylation status between 733 lung cancer patients and 694 nonmalignant controls with the pooled odds ratio being 6.02 (95% CI 3.17–11.42, Z=5.50, P<0.00001).Abbreviations: CI, confidence interval; M–H, Mantel–Haenszel test.
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f2-dddt-9-1785: The included studies investigated DAPK methylation status between 733 lung cancer patients and 694 nonmalignant controls with the pooled odds ratio being 6.02 (95% CI 3.17–11.42, Z=5.50, P<0.00001).Abbreviations: CI, confidence interval; M–H, Mantel–Haenszel test.

Mentions: In Figure 2, the first column has the study name; the second column is the proportion of DAPK methylation in lung cancers, and the third column is the proportion of DAPK methylation in normal controls. The weight in the fourth column is proportional to the inverse of the variance of the study (high variance, associated with a small study, meaning less weight is given to that study, and vice versa). The OR is shown numerically in the fifth column. In this case, the CI of the summary OR does not include 1.0 (it is 3.17–11.42), suggesting that the association is statistically significant. In the light of the “OR diagram” in the final column, the vertical line indicates an OR of 1.0. If DAPK methylation occurred more frequently in cancer tissue than in normal tissue, that would make the OR less than 1.0. The horizontal dots and bars represent the relative risk and 95% CI for each study. In summary, we observed that the frequency of DAPK methylation was significantly higher in lung cancer than in non-malignant lung tissues used as controls. The pooled OR from 13 studies including 733 lung cancer patients and 694 non-malignant lung tissues as controls shown in Figure 2 (OR 6.02, 95% CI 3.17–11.42, P<0.00001) indicates that inactivation of DAPK through methylation plays an important role in the pathogenesis of lung cancer. The overall methylation frequency of DAPK in lung cancer tissues was higher than that in normal controls, suggesting a potential role of DAPK methylation analysis in diagnosing lung cancer.


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

Li Y, Zhu M, Zhang X, Cheng D, Ma X - Drug Des Devel Ther (2015)

The included studies investigated DAPK methylation status between 733 lung cancer patients and 694 nonmalignant controls with the pooled odds ratio being 6.02 (95% CI 3.17–11.42, Z=5.50, P<0.00001).Abbreviations: CI, confidence interval; M–H, Mantel–Haenszel test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4378294&req=5

f2-dddt-9-1785: The included studies investigated DAPK methylation status between 733 lung cancer patients and 694 nonmalignant controls with the pooled odds ratio being 6.02 (95% CI 3.17–11.42, Z=5.50, P<0.00001).Abbreviations: CI, confidence interval; M–H, Mantel–Haenszel test.
Mentions: In Figure 2, the first column has the study name; the second column is the proportion of DAPK methylation in lung cancers, and the third column is the proportion of DAPK methylation in normal controls. The weight in the fourth column is proportional to the inverse of the variance of the study (high variance, associated with a small study, meaning less weight is given to that study, and vice versa). The OR is shown numerically in the fifth column. In this case, the CI of the summary OR does not include 1.0 (it is 3.17–11.42), suggesting that the association is statistically significant. In the light of the “OR diagram” in the final column, the vertical line indicates an OR of 1.0. If DAPK methylation occurred more frequently in cancer tissue than in normal tissue, that would make the OR less than 1.0. The horizontal dots and bars represent the relative risk and 95% CI for each study. In summary, we observed that the frequency of DAPK methylation was significantly higher in lung cancer than in non-malignant lung tissues used as controls. The pooled OR from 13 studies including 733 lung cancer patients and 694 non-malignant lung tissues as controls shown in Figure 2 (OR 6.02, 95% CI 3.17–11.42, P<0.00001) indicates that inactivation of DAPK through methylation plays an important role in the pathogenesis of lung cancer. The overall methylation frequency of DAPK in lung cancer tissues was higher than that in normal controls, suggesting a potential role of DAPK methylation analysis in diagnosing lung cancer.

Bottom Line: Death-associated protein kinase 1 (DAPK) is an important serine/threonine kinase involved in various cellular processes, including apoptosis, autophagy, and inflammation.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou, People's Republic of China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus